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Chromosome 1 aberrations in cancer
C h r o m o s o m e 1 Aberrations in Cancer Niels B. Atkin
ABSTRACT: Evidence for chromosome #1 involvemenl in structural rearrangements in cancer is reviewed. There have been adequate studies of cancer at most of the common sites, and at all of these, nonrandom chromosome #1 involvement has been demonstrated. In general, a variety of changes is encountered, irrespective of the site; most commonly, however, the changes result in the duplication of long arm material. It seems that these nonrandom changes, which" tend to occur at a relatively late stage, may contribute to the progression of all forms of cancer. However. a small number of chromosome #1 aberrations are also now known, which may represent specific and possibly initiating changes in particular forms of cancer. These include short arm deletions in neurohtastoma and translocations in leukemias and myelodys-
plasio. The literature contains n u m e r o u s reports of chromosome #1 aberrations in various types of h u m a n malignancy. This is often one of the two or three chromosomes that most frequently undergo structural changes in a given type of cancer. In an attempt Io document the extent of chromosome #1 i n v o l v e m e n t in cancer as a whole, I have assembled relevant reports relating to all the types of malignancy that so far appear to have been adequately studied (Table 1). I have not attempted to draw up a comprehensive list of all tile relevant papers, but merely show that there have been sufficient studies to demonstrate n o n r a n d o m chromosome #1 structural changes at each of the listed sites. Papers that only report findings on established cell lines have been excluded, because chromosome #1 changes may occur during culture [1]. Although some gaps are apparent in the list (there do not appear to have been adequate studies of carcinomas of the stomach or corpus uteri, for instance), there would still seem to be sufficient grounds for the assumption that chromosome #1 abnormalities play a role in the evolution of all types of malignancy. This would suggest that they are associated with an event that is c o m m o n to malignancy as a whole, rather than one that is restricted to neoplasms originating from a particular cell type (like the various tumor type-specific changes involving other chromosomes that have recently been described). Trisomy for bands lq25-1q32 was observed by Rowley [19] in 1977 to be the c o m m o n d e n o m i n a t o r in a series of patients with myeloproliferative disorders who had chromosome #1 aberrations, and subsequent studies have confirmed the frequent duplication of this region (or 1q21-1q32) not only in myeloproliferative disorders, but also in many other forms of cancer (Table 1). There is growing evidence, however, that, as well as chromosome #1 changes that are c o m m o n to all forms of
From the Departmentof Cancer Research, Mount VernonHospital, Northwood. Middlesex, England. Address requests for reprints to Dr. N. B. Atkin, Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, England. Received May 23, 1985; accepted ]uly 29. 1985.
279 ©1986 ElsevierSciencePublishingCo., Inc. 52 VanderbiltAve.. New York, NY 10017
Cancer Genet Cytogenet 21:279-285(1986) 0165-4608/86/$03.50
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N . B . Atkir
Table 1
S t u d i e s d e m o n s t r a t i n g n o n r a n d o m c h r o m o s o m e # 1 structural c h a n g e s in various types of m a l i g n a n c y
Tumor site/type Bladder/carcinoma Breast/carcinoma Bronchus/carcinoma Cervix uteri/carcinoma Colon and rectum/carcinoma Hepatoblastoma Kidney/Wilms' tumor Leukemias and myeloproliferative disorders
Lymphoma/Hodgkin's Lymphoma/non-Hodgkin's
Malignant nmlanoma Myeloma Neuroblastoma Neuroectodermal tumor/ primitive Ovary/carcinoma Prostate/carcinoma Retinoblastmna Sarcomas/soft tissue Testis
References Atkin and Baker [2]; Atkin and Baker [31 Ayraud el al. [4]; Kovat:s 151; Pathak [61: Rodgers el al. 171 Wurster-Hill and Maurer 18] Atkin and Baker 19]; Atkin and Baker [lOI; Atkin and Baker [11]: Kiricuta et el. 1121 Kovacs [51; Reichmann et al. [13] Douglass et al. 1141 Douglass et al. [151; Slater et al. [16]; Kaneko et al. [17]; Kondo et el. [181 Rowley [19]; Spriggs et al. ]20[; Papenhausen et al. [21]; Knuutila et al. [22]: Morris et al. [23]: Schmid et el. [24]; Slater et el. [25]; Bauchinger [26]; Alimena et al. [27]; Geraedts et al. [28]: q'omiyasu and Sasaki [29]: Pasquali et al. [301; Miyamoto et el. [31]: Mamaeva et al. [32] Hossfeld and Schmidt [33] Whang-Peng et al. [34]: Whang-Peng et el. [35]; Panani et el. [36]; Slavutsky et el. [37]: Kaneko et al. [38]; Fukuhara et al. 1391; Rowley and b'ukuhara I40]; Godde-Salz et el. [41]; (;aunt [42]; Mark et el. [431: Miyamoto et el. [441; Douglass et al. [45]; Yunis e el. [46] Becher et el. [47]; Balaban et al. [48]: Sandberg 149] Vermaelen et al. [50]: Liang et al. [51l; Wurster-Hill et al. [52]; l,ewi~ and MacKenzie [531 Gilbert et al. [1. 541; Brodeur et al. [55] Douglass et al. [14] Atkin and Pickthall [56]; Whang-Peng et al. [57]; Van der Riet-Fox e al. 1581 Atkin and Baker [59]: Atkin and Baker [60] Benedict et al. [61]; Gardner et al. [62], Chaum et al. [63]; Kusnetsova et el. [64] Becher et al. [651: Douglass et al. [141; Tren! et al. {66] Atkin and Baker 167]
cancer, there are a n u m b e r of o t h e r n o n r a n d o m c h a n g e s that are specific for partic ular neoplasias. T h u s , l p i n w ~ l v e m e n t has b e e n d e s c r i b e d in n e u r o b l a s t o m a (se below), t(1;19}(q23;p13.3) in a c u t e l y m p h o c y t i c l e u k e m i a [68], t(1;3}(p36;q21) [6 (. and t ( 1 ; 7 ) ( p l l ; p 1 1 ) [28, 70] in a c u t e n o n l y m p h o c y t i c l u e k e m i a and myelodyspl~ sia, and t(1;17}(pll:q11) in the blastic p h a s e of c h r o n i c m y e l o i d l e u k e m i a [30]. In c a n c e r generally, c h r o m o s o m e #1 b r e a k p o i n t s are s o m e w h a t variable, but ha of those d e s c r i b e d in a series of 218 m a l i g n a n c i e s w e r e s i t u a t e d in or near th c e n t r o m e r i c h e t e r o c h r o m a t i n [71]. T h e l q + c h r o m o s o m e s , w i t h one or t w o dupl cations of part of the long arm, are c o m m o n and, if the break is t h r o u g h h e t e r o c h n matin, o n e or two interstitial C - b a n d s m a y be present on the long arm (e.g., i c a r c i n o m a s of the b l a d d e r [3]). That the significant c h a n g e is d u p l i c a t i o n of lot arm material, rather than the loss of short arm material or the o c c u r r e n c e of breal age in the short arm (both of w h i c h are c o m m o n e v e n t s in tumors), m a y be su: gested by the o b s e r v a t i o n that m a l i g n a n c i e s in w h i c h c h r o m o s o m e #1 aberratior are absent m a y instead h a v e t r i s o m y for this c h r o m o s o m e , e.g., myeloproliferatix d i s o r d e r s [27, 72] and c a r c i n m n a of the c e r v i x uteri [10]. Apart from the few specific c h a n g e s a l r e a d y m e n t i o n e d , c h r o m o s o m e changes in cancer, i r r e s p e c t i v e of site or cell type, may be s u m m a r i z e d as follow
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In a proportion of neoplasias at a given site, no structural aberrations are found, but such neoplasias may show trisomy 1, or a relative excess of c h r o m o s o m e s #1. where the c h r o m o s o m e n u m b e r is high. Where present, structural changes commonly (though not invariably] result in an excess of long arm material. The 1 p chromosomes are c o m m o n and, in near-diploid neoplasias, are usually accompanied by at least two normal (t)r abnormal) c h r o m o s o m e s #1 (e.g., in carcinomas of the bladder [2] and cervix uteri [91). Other types of abnormal c h r o m o s o m e #1 may be a c c o m p a n i e d by one, two or more normal (or abnormal} chromosomes #1; among these abnormal chromosomes, long arm isochromosomes are common, as is the a d d i t i o n of material from lq or from other c h r o m o s o m e s to either arm of a c h r o m o s o m e #1. Aberrations less often encountered are short arm isochromosomes and long arm deletions. In neuroblastomas, the loss or rearrangement of material on the c h r o m o s o m e #1 short arm was found in over 70% of tumors, the most frequent breakpoint being lp32, and it was suggested that the loss of activity of one or more genes on the distal part of l p (distal to lp31} may be important in tile d e v e l o p m e n t of neuroblastomas, in which deletions of l p are common, but trisomy for any portion of c h r o m o s o m e #1 is rare [1, 54]. A d d i t i o n a l c h r o m o s o m e # l long arm material was, however, present in 37% of the tumors Ill and may represent a late change that is related to tumor progression. It has frequently been suggested that c h r o m o s o m e #1 aberrations are relatively late events in malignant progression. Thus, they are rarely present in the chronic phase of chronic myeloid leukemia, whereas they are not u n c o m m o n in the acute phase and may indicate a poor prognosis 132]. However, c h r o m o s o m e #1 aberrations in chronic m y e l o i d leukemia may be related to previous treatment; in one interesting report [73], they were found in patients who had been treated in the chronic phase by intensive t:hemotherapy, but not in those treated by b u s u l p h a n alone. Although data on the preinvasive phase of carcinomas are scanty, two reports indicate that c h r o m o s o m e #1 structural changes may precede stromal invasion in the cervix uteri 112, 74J. In one of these reports ]741, the aberration found in both a carcinoma in situ and a carcinoma in situ with a small focus of invasive tumor was the relatively u n c o m m o n l q - anomaly. Both these lesions had near-triploid modes, and the chromosome #1 markers were present in duplicate. Quite frequently, however, invasive tumors with near-triploid or h y p o t e t r a p l o i d modes have only single copies of c h r o m o s o m e #1 markers (although two or three different markers may be present}, e.g., in the cervix uteri [11J, b l a d d e r [3], and prostate [60], indicating that either the markers a p p e a r e d after the evolving neoplastic stemline underwent c h r o m o s o m a l doubling, or (perhaps less likely) they had taken part in a chromosomal doubling, but one of the d u p l i c a t e d markers had subsequently been lost. Four oncogenes have been assigned to c h r o m o s o m e # 1 : N - r a s - 1 (to l p l l - p 1 3 I75]), Blym-1 ( l p 3 2 [76]), c-src ( l p 3 4 - p 3 6 [771, and SK (1q12-qter [78]). Also, four "constitutive" fragile sites have been located on c h r o m o s o m e #1 (1p31.2, p21.2, q21.3, and q44.1) [79]. W. F. Benedict et al. 180] found that, in near-tetraploid hybrids between a h u m a n fibrosarcoma cell line (which contains an activated N-ras-1) and normal fibroblasts, a loss of c h r o m o s o m e #1 was correlated with the reexpression of tumorigenicity. As a possible mechanism for this reexpression they suggested the loss of a gene present in the normal fibroblasts that could suppress tumorigenicity (perhaps by specifically regulating the expression of the activated N-ras-1, gene); this gene might be the normal N-ras-I allele. Malignancy was not s u p p r e s s e d in near-hexaploid hybrids that contained an a p p r o x i m a t e l y doubled fibrosarcoma and a single normal fibroblast c h r o m o s o m e complement, suggesting that the tumorigenicity is chromo-
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N.B. Aik s o m a l l y dosage d e p e n d e n t . In a n o t h e r recent s t o d y [81], r e e x p r e s s i o n of transf~ m a t i o n in hybrids b e l w e e n t r a n s f o r m e d baby h a m s t e r k i d n e y cells and h u m a n broblasts was a s s o c i a t e d w i t h loss of h u m a n c h r o m o s o m e # 1 , again suggestin~ s u p p r e s s o r role for this c h r o m o s o m e in m a l i g n a n c y . In v i e w of the possibility tl m a l i g n a n c y m a y d e p e n d on a gene dosage effect d e t e r m i n e d by the n u m b e r of cc ies of an a c t i v a t e d gene, c o m p a r e d w i t h t h o s e of a s u p p r e s s o r gene (perhaps t n o r m a l allele) on the h o m o l o g o u s c h r o m o s o m e , and in the light of e v i d e n c e t| h o m o z y g o s i t y or h e m i z y g o s i t y for r e c e s s i v e genes m a y be an i m p o r t a n t charact, istic of the cells of at least s o m e t u m o r s [82[, it is of interest to d e t e r m i n e from t s t u d y of h e t e r o c h r o m a t i n and e n z y m e p o l y m o r p h i s m s w h e t h e r , for instance, t aberrant and n o r m a l c h r o m o s o m e s #1 are d e r i v e d from the s a m e or different hon logs and w h e t h e r or not there is e v i d e n c e for the o c c u r r e n c e of s o m a t i c crossingo~ b e t w e e n the h o m o l o g s , as has been f o u n d for c h r o m o s o m e # 1 3 in cell lines deriv from testicular t u m o r s [831 and in r e t i n o b l a s t o m a s [84[. In c o n c l u s i o n , it s e e m s that c h r o m o s o m e #1 structural c h a n g e s are c o m m o n most, and probably all, forms of cancer, that t h e y o c c u r r e l a t i v e l y late in the coul of d e v e l o p m e n t of the n e o p l a s t i c stem line (although they m a y be p r e s e n t at i stage of, 0I" p r e c e d e , c o m m e n c i n g stromal i n v a s i o n l , and that a l t h o u g h it is possil that d u p l i c a t i o n of a g e n e or genes on the long arm is the significant event, in least s o m e types of n e o p l a s i a , breakage or loss i n v o l v i n g the short arm (in neu b l a s t o m a [1]) or specific t r a n s l o c a t i o n s (in l e u k e m i a s anti related disorders) are a important. 1 thank Miss Marion C. Baker for critically reading the manuscript and Mrs. B. I. Laogdon secretarial services.
REFERENCES 1. Gilbert F, Feder M, Balaban G, Brangman D, Lurie OK, Podolsky R, Rinaldt V. Vinikq N, Weisband I (1984): ttuman neuroblastomas and abnormalities of chromosomes 1 a 17. Cancer Res 44:5444-5449. 2. Atkin NB, Baker MC (1977): Abnormal chromosomes and number 1 heterochromatin ,, iants revealed in C-banded preparations from 13 bladder carcinomas. Cytobios 18:1t 109.
3. Atkin NB, Baker ME: (1985): Cytogenetic study of ten carcinomas of the bladder: lnvol ment of chromosomes 1 and 11. Cancer Genet Cytogenet 15:253-268. 4. Ayraud N, Lambert IC, Hufferman-Tribollei K, Basteris B (1977): A comparative cyte uetic study of seven carcinomas of mammary origin. Ann Genet 20:171-177. 5. Kovacs G (1978): Abnormalities of chromosome No. 1 in human solid malignant tumor Int J Cancer 21:688-694. 6. Pathak S (19801: Cytogenetic analysis in human breast tumors. Cancer Genet Cytoge 1:281-289. 7. Rodgers CS, Hill SM, Hult~n MA (1984): Cytogenetic analysis in human breast carcinol 1. Nine cases in the diploid range investigated using direct preparations. Cancer Ge Cytogenet 13:95-119. 8. Wurster-Hill Dtl, Maurer LH (1978): Cytogenetic diagnosis of cancer: Abnormalitie., chromosomes and polyploid levels in the bone marrow of patients with small cell a plastic carcinoma of the lung. J Nail ('ancer Inst 61:1065-1075. 9. Atkin NB, Baker MC (1979): Chrolnosome 1 in 26 carcinomas of the cervix uteri. Stl rural and numerical changes. Cancer 44:604-613. 10. Atkin NB, Baker MC (1982): Nonrandom chromosome changes in carcinoma of the cel uteri. I. Nine near-diploid tumors. Cancer Genet Cytogenet 7:209--222. 11. Atkin NB, Baker MC (1984): Nonrandom chromosome changes in carcinoma of the cel uteri. 11. Ten tumors in the triploid--tetraploid range. Cancer Genet Cylogenet 13:189-~
~1 A b e r r a t i o n s in C a n c e r
283
12. Kiricuta l, Suciu St, Giurgiuman M (1982): Chromosomenver~inderungen bei 20 L~isionen der Cervix uteri. Arch Geschwulstforsch 52:205-211. 13. Reichmann A, Martin P, Levin B (1984): Chromosomes in human large bowel tumors. A study of chromosome 1. Cancer Genet Cytogenet 12:295-301. 14. Douglass EC, Green AA, ttayes FA, Etcubanas E, Horowitz M, Wilimas J (1984): Chromosome 1 abnormalities: A common feature of pediatric solid tumors. Proc Annu Meet Am Assoc Cancer Res 25:37. 15. Douglass EC, Wilimas JA, Green AA, Look AT (1985}: Abnormalities of chromosomes 1 and 11 in Wilms' tumor. Cancer Genet Cytogenet 14:331-338. 16. Slater RM, de Kraker J, Voute PA, Delemarre JFM {1985): A cytogenetic study of Wilms' tumor. Cancer Genet Cytogenet 14:95-109. 17. Kaneko Y, Kondo K, Rowley JD, Moehr JW, Maurer HS (1983): Further chromosome studies on Wilms' tumor cells of patients without aniridia. Cancer Genet Cytogenet 10:191197. 18. Kondo K, Chilcote RR, Maurer HS, Rowley JD (1984): Chromosome abnormalities in tumor cells from patients with sporadic Wilms' tumor. Cancer Res 44:5376-5381. 19. Rowley JD (1977): Mapping of human chromosomal regions related to neoplasia: Evidence from chromosomes 1 and 17. Proc Natl Acad Sci USA 74:5729-5733. 20. Spriggs At, Holt JM, Bedford J (1976): Duplication of part of the long arm of chromosome 1 in marrow cells of a treated case of myelomatosis. Blood 48:595-599. 21. Papenhausen PR, Wolkin-Friedman E, Pekzar-Wissner C (1984): Novel tandem triplication of l q in a patient with a myelodysplastic syndrome. Cancer Genet Cytogenet 12:145-150. 22. Knuutila S, Ruutu T, Partanen S, Vuopio P (1983): Chromosome l q + in erythroid and granulocyte-monocyte precursors in a patient with essential thrombocythemia. Cancer Genet Cytogenet 9:245-249. 23. Morris CM, Fitzgerald PH, Neville MA, Wyld PJ, Beard MEJ (1984): Does multisomy of chromosome lq confer a proliferative advantage in B-cell acute lymphoblastic leukemia? Cancer 54:48-53. 24. Schmid E, K6hler J (1984): Involvement of chromosomes 1 and 11 in three cases with myeloproliferative diseases. Cancer Genet Cytogenet 11:121-123. 25. Slater RM, Philip P, Badsberg E, Behrendt H, Hansen NE, Van Heerde P (1979): A 14q + chromosome in a B-cell acute lymphocytic leukemia and in a case of leukemic non-endemic Burkitt lymphoma. Int ] Cancer 23:639--647. 26. Bauchinger M {1984): Trisomy lq and loss of Y chromosome in a male with osteomyelosclerosis. Acta Haematol 72:131-134. 27. Alimena G, Dallapiccola B, Mitelman F, Montuoro A (1980): Aberrations of chromosome No. 1 in blastic phase of chronic myeloid leukemia. Hereditas 92:59-63. 28. Geraedts JPM, Den Ottolander GJ, Ploem JE, Muntinghe OG (1980): An identical translocation between chromosome 1 and 7 in three patients with myelofibrosis and myeloid metaplasia. Br J Haematol 44:569-575. 29. Tomiyasu T, Sasaki M (1981): Atypical myelofibrosis associated with a partial duplication of the long arm of chromosome 1. Chromosome Information Service No. 31, pp 35-36. 30. Pasquali F, Francesconi D, Casalone R, lppoliti G (1979): Partial trisomy 1 due to 1/17 translocation in Phi-positive chronic myelocytic leukemia. Hum Genet 49:277-282. 31. Miyamoto K, Hamasaki K, Kitajima K, Adachi T, Tanaka T, Sato J (1981): Abnormalities of chromosome No. I related to blood dyscrasias: Study of 10 cases. Acta Med Okayama 35:137-141. 32. Mamaeva SE, Mamaev NN, Jartseva NM, Belyaeva LV, Scherbakova EG (1983): Complete or partial trisomy for the long arm of chromosome 1 in patients with various hematologic malignancies. Hum Genet 63:107-112. 33. Hossfeld DK, Schmidt CG (1978): Chromosome findings in effusions from patients with Hodgkin's disease. Int J Cancer 21:147-156. 34. Whang-Peng J, Bunn PA Jr, Knutsen T, Matthews MJ, Schechter G, Minna JD (1982): Clinical implications of cytogenetic studies in cutaneous T-cell lymphoma (CTC!,) Cancer 50:1539-1553. 35. Whang-Peng J, Lee EC, Sieverts H, Magrath IT (1984): Burkitt~s lymphoma in AIDS: Cytogenetic study. Blood 63:818.-822.
284
N . B . Atl
36. Panani A, Ferti-Passantonopoulou A, Dervenoulas J (1984): Partial duplication of lq i malignant lymphoma. Cancer Genet Cytogenet 11:87-90. 37. Slavutsky 1, Labal de Vinuesa M, Dupnnt J, Mondini N, Brieux de Salum S (1981): Abn malities of chromosome No. 1: Two cases with lymphocytic Iymphomas. Cancer Ge Cytogenet 3:341-346. 38. Kaneko K, Variakojis D, Kluskens L, Rowley JD (1982): Lymphoblastic lymphoma: C~ genetic, pathologic, and immunologic studies, lnl J Cancer 30:273-279. 39. Fukuhara S, Rowley JD, Variakojis D, Golomb HM (1979): Chromosome abnormalities poorly differentiated lymphocytic lymphoma. Cancer Res 39:3119-3128. 40. Rowley JD, Fukuhara S (1980): Chromosome studies in non-Hodgkin's lymphomas. Se~ Oncol 7:255-266. 41. G6dde-Salz E, Schwarze EW, Stein H, Lennert K, Grote W (1981): Cytogenetic findings T-zone lymphoma. J Cancer Res Clin Oncol 101:81-89. 42. Gaunt KL (1981): Non-random chromosome involvement in non-Burkitt, non-HodgJ lymphoma. Br J Cancer 44:930. 43. Mark J, Ekedahl C, Dahlenfors R (1978): Characteristics of the banding patterns in n~ Hodgkin and non-Burkitt lymphomas. Hereditas 88:229-242. 44. Miyamoto K, Miyano K, Miyoshi I, Hamasaki K, Nishihara R, Terao S, Kimura I, Ma~ K, Matsumura K, Nishijima K, Tanaka T (1980): Chromosome 14q + in a Japanese pati~ with Burkitt's lymphoma. Acta Med Okayama 34:61-65. 45. Douglass EC, Magrath IT, Lee EC, Whang-Peng J (1980]: Cytogenetic studies in non-A can Burkitt lymphoma. Blood 55:148-155. 46. Yunis JJ, Oken MM. Theologides A, Howe RB, Kaplan ME (1984}: Recurrent chromosot defects are found in most patients with non-Hodgkin's lymphoma. Cancer Genet Cyto net 13:17-28. 47. Becher R, Gibas Z, Karakousis C, Sandberg AA (1983): Nonrandom chromosome char in malignant melanoma. Cancer Res 43:5010-5016. 48. Balaban G, Herlyn M, Guerry D IV, Bartolo R, Koprowski H, Clark WH, Nowell PC {19~ Cytogenetics of h u m a n malignant melanoma and premalignant lesions. Cancer Genet I togenet 11:429-439. 49. Sandberg AA (1980}: The Chromosomes in Human Cancer and l.eukemia. Elsevier No Holland, New York. 50. Vermaelen K, Story P, Bosly A, Vail den Berghe H (1983): Translocation t(6:9) in a c of multiple myeloma. Ann Genet 26:56-57. 51. Liang W, Hopper JE, Rowley JD (1979): Karyotype abnormalities and clinical aspect~ patients with multiple myeloma and related paraproteinemic disorders. Cancer 44:6: 644. 52. Wurster-Hill DH, Mclntyre OR, Cornwell GG III (1978): Chromosome studies in myelt atosis. Virchows Arch B Cell Pathol 29:93-97. 53. Lewis JP, MacKenzie MR (1984): Multiple myeloma is associated with nonrandom c/~ mosomal abnormalities. Proc Annu Meet Am Soc Clin Oncol 3:9. 54. Gilbert F, Balaban G, Moorhead P, Bianchi D. Schlesinger H (1982): Abnormalities of c| mosome l p in h u m a n neuroblastoma tumors and cell lines. Cancer Genet Cytogenet 7:: 42. 55. Brodeur GM, Green AA, Hayes FA, Williams KJ, Williams DL, Tsiatis AA (1981): Cyic netic features of h u m a n neuroblastomas and cell lines. Cancer Res 41:4678-4686. 56. Atkin NB, Pickthall VJ (1977): Chromosomes 1 in 14 ovarian cancers. Heterochrom~ variants and structural changes. Hum Genet 38:25-33. 57. Whang-Peng J, Knutsen T, Douglass EC, Chu E, Ozols RF, Hogan WM, Young RC (19~ Cytogenetic studies in ovarian cancer. Cancer Genet Cytogenet 11:91-106. 58. Van der Riet-Fox MF, Retie[ AE, Van Niekerk WA (1979}: Chromosome changes in h u m a n neoplasms studied with banding. Cancer 44:2108-2119. 59. Atkin NB, Baker MC (1985}: Chromosome 10 deletions in carcinoma of the prostate Engl J Med 312:315. 60. Atkin NB, Baker MC (1985}: Chromosome study of five cancers of the prostate. Ilum G~ 70:359-364.
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61. Bc'm.'dict WF, Banerjc'e A. Mark C. Murphree AL (1983): Nonrandom chromosomal changes in untreated retinoblastomas. Cancer (.;enet Cytogenet 10:311--333. 62. Gardner HA. Gallie BL, Kl~ight LA, Phillips RA 11982): Multiple karyotypic changes in retinoblastoma tumor cells: Presence of normal chromosome No. 13 in most tumors. Cancer (;enet Cyt()gem.q 6:201 2 ! 1. 63. Chaum E. Ellsworth RM, Abramson I)H, Haik BG. Kitchin FD, Chaganti RSK (1984l: Cytogenetic analysis of retinoblastoma: Evidence for multifocal origin and in r i v e gene amplification. Cytogenetic Cel) (;enet 38:82-91. 64. Kusnetsova I,E, Prigogina EL. Pogosianz liE. Belkina HM (19821: Similar chromosomal abnormalities in several retinoblastomas, l lure Genet 61:201 -204. 65. Becher R, Wake N, Gibas Z, Ochi 1I. Sandberg AA [1984): (]hromosome changes in soft tissue sarcomas. Proc Annu Meet Am Assoc Cancer Res 25:36. 66, Trent JM. Meltzer PS, Thompson FH, Casper iT. Fogh )E [1984): Nonrandom chromosome alterations in rhabdomyosar(:oma (RMS/: Possible association with a ras-related oncogene. Proc Annu Meet Am Asset: Cancer Res 25:66. 67. Atkin Nil, Baker MC (1985): Chromostmle analysis of three seminontas. Cancer (;enet Cytoge.net 17:315- 323. 68. Michael PM, Garson OM. Calhm DI" (1!}85}: A review of the t(l;19] breakpoints in acute Iymphoc'~,tic leukemia. Cancer Genet Cytogent;t 17:79-8(}. 69. Moir DJ, ]ones PAE. Pearson I, Duncan IR, Cook P, Buckle VJ (19841: A new translacation, t(l:3)(p36;q21), in myelodysplastic disorders. Blood 64:553--555. 70. Scheres IMJC, Hustinx ']'Wl, IIoldrinet RS(.;, Geraedts JPM, Hagemeijer A, van der BlijPhilipsen M (1984): Translocation 1:7 in dyshematopoiesis: Possibly induced with a nonrandom geographit: distribution. Cancer Gem;t ('ytogenet 12:283--294. 71. Brito-Bahapulle V, Atkin NB (1981): Breakpoints in chromosome 1 abnormalities of 218 human neoplasms. Cancer (;enet Cytogenet 4:215-225. 72. Rowley JD [19751: Abnormalities of chromosr~me l in myeloproliferative disorders. Cancer 36:1748-1758. 73. Alimena G, Brandt L, Dallapiccola B, Mitehnan F, Nilsson PG (1979]: Secondary chromosome changes in chronic myeloid leukemia: Relation to treatment. Cancer Genet Cytogenet 1:79-85. 74. Atkin NB, Baker MC, Eerti-Passantonopoulou A (19831: Chrontosome changes in early gynecologic malignancies. At:ta Cytol 27:450-453. 75. Rahin M. Watson M. Barker PE, Ryan J, Breg WR. Ruddle 1.'I-t (19841: NRAS transforming gene maps to region p l l - - , p l 3 on chromosome 1 by in situ hybridization. Cytogenet Cell Genet 38:70-72. 76. Morton ('C. Taub R. Diamond A, Lane MA. Cooper (;M. Leder P (1984): Mapping of the human Blym-1 transforming gene activated in Burkitt lymphomas to chromosome 1. Science 223:173-175. 77. Le Beau MM, Westbrook CA. l)iaz MO, Rowley ID (19841: Evidence for two distinct c-src loci on human chromosomes 1 and 20. Nature 312:70-71. 78. Balazs I, Grzeschik KI'I, Stavnezer E (1984]: Assignment of the human homologue of a chicken oncogene to chromosome 1. Cytogenet Cell Genet 37:410-411. 79. Yunis JJ, Soreng AI, (19841: Constitutive fragile sites and cancer. Science 226:1199.-1204. 80. Benedict WE. Weissman BE. Mark C. Stanbridge El (1984): Tunmrigenicity of human ttT1080 fibrosarcoma X normal fibroblast hybrids: ('hromosome dosage dependency. Cancer Res 44:3471-3479. 81. Stoler A, Bouck N [1985): Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transl~ormation. Proc Natl Acad Sci USA 82:570-574. 82, Murphree AI,. Benedict WF (19841: Retinoblastoma: Clues to human oncogenesis. Science 223:1028-1(133. 83. Parrington JM, West LF [1985): Loss of chromosome and enzyme markers in cultures from testicular tumt~urs. Clin Genet 27:326 (ahstr}. 84. Cavenee WK, I)ryja TP, Phillips RA, Benedict WE, Godbout R, Gallic BL, Murphree AL, Strong LC, White RL [1983): Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779-784.
ABSTRACT: Evidence for chromosome #1 involvemenl in structural rearrangements in cancer is reviewed. There have been adequate studies of cancer at most of the common sites, and at all of these, nonrandom chromosome #1 involvement has been demonstrated. In general, a variety of changes is encountered, irrespective of the site; most commonly, however, the changes result in the duplication of long arm material. It seems that these nonrandom changes, which" tend to occur at a relatively late stage, may contribute to the progression of all forms of cancer. However. a small number of chromosome #1 aberrations are also now known, which may represent specific and possibly initiating changes in particular forms of cancer. These include short arm deletions in neurohtastoma and translocations in leukemias and myelodys-
plasio. The literature contains n u m e r o u s reports of chromosome #1 aberrations in various types of h u m a n malignancy. This is often one of the two or three chromosomes that most frequently undergo structural changes in a given type of cancer. In an attempt Io document the extent of chromosome #1 i n v o l v e m e n t in cancer as a whole, I have assembled relevant reports relating to all the types of malignancy that so far appear to have been adequately studied (Table 1). I have not attempted to draw up a comprehensive list of all tile relevant papers, but merely show that there have been sufficient studies to demonstrate n o n r a n d o m chromosome #1 structural changes at each of the listed sites. Papers that only report findings on established cell lines have been excluded, because chromosome #1 changes may occur during culture [1]. Although some gaps are apparent in the list (there do not appear to have been adequate studies of carcinomas of the stomach or corpus uteri, for instance), there would still seem to be sufficient grounds for the assumption that chromosome #1 abnormalities play a role in the evolution of all types of malignancy. This would suggest that they are associated with an event that is c o m m o n to malignancy as a whole, rather than one that is restricted to neoplasms originating from a particular cell type (like the various tumor type-specific changes involving other chromosomes that have recently been described). Trisomy for bands lq25-1q32 was observed by Rowley [19] in 1977 to be the c o m m o n d e n o m i n a t o r in a series of patients with myeloproliferative disorders who had chromosome #1 aberrations, and subsequent studies have confirmed the frequent duplication of this region (or 1q21-1q32) not only in myeloproliferative disorders, but also in many other forms of cancer (Table 1). There is growing evidence, however, that, as well as chromosome #1 changes that are c o m m o n to all forms of
From the Departmentof Cancer Research, Mount VernonHospital, Northwood. Middlesex, England. Address requests for reprints to Dr. N. B. Atkin, Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex HA6 2RN, England. Received May 23, 1985; accepted ]uly 29. 1985.
279 ©1986 ElsevierSciencePublishingCo., Inc. 52 VanderbiltAve.. New York, NY 10017
Cancer Genet Cytogenet 21:279-285(1986) 0165-4608/86/$03.50
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N . B . Atkir
Table 1
S t u d i e s d e m o n s t r a t i n g n o n r a n d o m c h r o m o s o m e # 1 structural c h a n g e s in various types of m a l i g n a n c y
Tumor site/type Bladder/carcinoma Breast/carcinoma Bronchus/carcinoma Cervix uteri/carcinoma Colon and rectum/carcinoma Hepatoblastoma Kidney/Wilms' tumor Leukemias and myeloproliferative disorders
Lymphoma/Hodgkin's Lymphoma/non-Hodgkin's
Malignant nmlanoma Myeloma Neuroblastoma Neuroectodermal tumor/ primitive Ovary/carcinoma Prostate/carcinoma Retinoblastmna Sarcomas/soft tissue Testis
References Atkin and Baker [2]; Atkin and Baker [31 Ayraud el al. [4]; Kovat:s 151; Pathak [61: Rodgers el al. 171 Wurster-Hill and Maurer 18] Atkin and Baker 19]; Atkin and Baker [lOI; Atkin and Baker [11]: Kiricuta et el. 1121 Kovacs [51; Reichmann et al. [13] Douglass et al. 1141 Douglass et al. [151; Slater et al. [16]; Kaneko et al. [17]; Kondo et el. [181 Rowley [19]; Spriggs et al. ]20[; Papenhausen et al. [21]; Knuutila et al. [22]: Morris et al. [23]: Schmid et el. [24]; Slater et el. [25]; Bauchinger [26]; Alimena et al. [27]; Geraedts et al. [28]: q'omiyasu and Sasaki [29]: Pasquali et al. [301; Miyamoto et el. [31]: Mamaeva et al. [32] Hossfeld and Schmidt [33] Whang-Peng et al. [34]: Whang-Peng et el. [35]; Panani et el. [36]; Slavutsky et el. [37]: Kaneko et al. [38]; Fukuhara et al. 1391; Rowley and b'ukuhara I40]; Godde-Salz et el. [41]; (;aunt [42]; Mark et el. [431: Miyamoto et el. [441; Douglass et al. [45]; Yunis e el. [46] Becher et el. [47]; Balaban et al. [48]: Sandberg 149] Vermaelen et al. [50]: Liang et al. [51l; Wurster-Hill et al. [52]; l,ewi~ and MacKenzie [531 Gilbert et al. [1. 541; Brodeur et al. [55] Douglass et al. [14] Atkin and Pickthall [56]; Whang-Peng et al. [57]; Van der Riet-Fox e al. 1581 Atkin and Baker [59]: Atkin and Baker [60] Benedict et al. [61]; Gardner et al. [62], Chaum et al. [63]; Kusnetsova et el. [64] Becher et al. [651: Douglass et al. [141; Tren! et al. {66] Atkin and Baker 167]
cancer, there are a n u m b e r of o t h e r n o n r a n d o m c h a n g e s that are specific for partic ular neoplasias. T h u s , l p i n w ~ l v e m e n t has b e e n d e s c r i b e d in n e u r o b l a s t o m a (se below), t(1;19}(q23;p13.3) in a c u t e l y m p h o c y t i c l e u k e m i a [68], t(1;3}(p36;q21) [6 (. and t ( 1 ; 7 ) ( p l l ; p 1 1 ) [28, 70] in a c u t e n o n l y m p h o c y t i c l u e k e m i a and myelodyspl~ sia, and t(1;17}(pll:q11) in the blastic p h a s e of c h r o n i c m y e l o i d l e u k e m i a [30]. In c a n c e r generally, c h r o m o s o m e #1 b r e a k p o i n t s are s o m e w h a t variable, but ha of those d e s c r i b e d in a series of 218 m a l i g n a n c i e s w e r e s i t u a t e d in or near th c e n t r o m e r i c h e t e r o c h r o m a t i n [71]. T h e l q + c h r o m o s o m e s , w i t h one or t w o dupl cations of part of the long arm, are c o m m o n and, if the break is t h r o u g h h e t e r o c h n matin, o n e or two interstitial C - b a n d s m a y be present on the long arm (e.g., i c a r c i n o m a s of the b l a d d e r [3]). That the significant c h a n g e is d u p l i c a t i o n of lot arm material, rather than the loss of short arm material or the o c c u r r e n c e of breal age in the short arm (both of w h i c h are c o m m o n e v e n t s in tumors), m a y be su: gested by the o b s e r v a t i o n that m a l i g n a n c i e s in w h i c h c h r o m o s o m e #1 aberratior are absent m a y instead h a v e t r i s o m y for this c h r o m o s o m e , e.g., myeloproliferatix d i s o r d e r s [27, 72] and c a r c i n m n a of the c e r v i x uteri [10]. Apart from the few specific c h a n g e s a l r e a d y m e n t i o n e d , c h r o m o s o m e changes in cancer, i r r e s p e c t i v e of site or cell type, may be s u m m a r i z e d as follow
#1 Aberrations in Canc:er
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In a proportion of neoplasias at a given site, no structural aberrations are found, but such neoplasias may show trisomy 1, or a relative excess of c h r o m o s o m e s #1. where the c h r o m o s o m e n u m b e r is high. Where present, structural changes commonly (though not invariably] result in an excess of long arm material. The 1 p chromosomes are c o m m o n and, in near-diploid neoplasias, are usually accompanied by at least two normal (t)r abnormal) c h r o m o s o m e s #1 (e.g., in carcinomas of the bladder [2] and cervix uteri [91). Other types of abnormal c h r o m o s o m e #1 may be a c c o m p a n i e d by one, two or more normal (or abnormal} chromosomes #1; among these abnormal chromosomes, long arm isochromosomes are common, as is the a d d i t i o n of material from lq or from other c h r o m o s o m e s to either arm of a c h r o m o s o m e #1. Aberrations less often encountered are short arm isochromosomes and long arm deletions. In neuroblastomas, the loss or rearrangement of material on the c h r o m o s o m e #1 short arm was found in over 70% of tumors, the most frequent breakpoint being lp32, and it was suggested that the loss of activity of one or more genes on the distal part of l p (distal to lp31} may be important in tile d e v e l o p m e n t of neuroblastomas, in which deletions of l p are common, but trisomy for any portion of c h r o m o s o m e #1 is rare [1, 54]. A d d i t i o n a l c h r o m o s o m e # l long arm material was, however, present in 37% of the tumors Ill and may represent a late change that is related to tumor progression. It has frequently been suggested that c h r o m o s o m e #1 aberrations are relatively late events in malignant progression. Thus, they are rarely present in the chronic phase of chronic myeloid leukemia, whereas they are not u n c o m m o n in the acute phase and may indicate a poor prognosis 132]. However, c h r o m o s o m e #1 aberrations in chronic m y e l o i d leukemia may be related to previous treatment; in one interesting report [73], they were found in patients who had been treated in the chronic phase by intensive t:hemotherapy, but not in those treated by b u s u l p h a n alone. Although data on the preinvasive phase of carcinomas are scanty, two reports indicate that c h r o m o s o m e #1 structural changes may precede stromal invasion in the cervix uteri 112, 74J. In one of these reports ]741, the aberration found in both a carcinoma in situ and a carcinoma in situ with a small focus of invasive tumor was the relatively u n c o m m o n l q - anomaly. Both these lesions had near-triploid modes, and the chromosome #1 markers were present in duplicate. Quite frequently, however, invasive tumors with near-triploid or h y p o t e t r a p l o i d modes have only single copies of c h r o m o s o m e #1 markers (although two or three different markers may be present}, e.g., in the cervix uteri [11J, b l a d d e r [3], and prostate [60], indicating that either the markers a p p e a r e d after the evolving neoplastic stemline underwent c h r o m o s o m a l doubling, or (perhaps less likely) they had taken part in a chromosomal doubling, but one of the d u p l i c a t e d markers had subsequently been lost. Four oncogenes have been assigned to c h r o m o s o m e # 1 : N - r a s - 1 (to l p l l - p 1 3 I75]), Blym-1 ( l p 3 2 [76]), c-src ( l p 3 4 - p 3 6 [771, and SK (1q12-qter [78]). Also, four "constitutive" fragile sites have been located on c h r o m o s o m e #1 (1p31.2, p21.2, q21.3, and q44.1) [79]. W. F. Benedict et al. 180] found that, in near-tetraploid hybrids between a h u m a n fibrosarcoma cell line (which contains an activated N-ras-1) and normal fibroblasts, a loss of c h r o m o s o m e #1 was correlated with the reexpression of tumorigenicity. As a possible mechanism for this reexpression they suggested the loss of a gene present in the normal fibroblasts that could suppress tumorigenicity (perhaps by specifically regulating the expression of the activated N-ras-1, gene); this gene might be the normal N-ras-I allele. Malignancy was not s u p p r e s s e d in near-hexaploid hybrids that contained an a p p r o x i m a t e l y doubled fibrosarcoma and a single normal fibroblast c h r o m o s o m e complement, suggesting that the tumorigenicity is chromo-
282
N.B. Aik s o m a l l y dosage d e p e n d e n t . In a n o t h e r recent s t o d y [81], r e e x p r e s s i o n of transf~ m a t i o n in hybrids b e l w e e n t r a n s f o r m e d baby h a m s t e r k i d n e y cells and h u m a n broblasts was a s s o c i a t e d w i t h loss of h u m a n c h r o m o s o m e # 1 , again suggestin~ s u p p r e s s o r role for this c h r o m o s o m e in m a l i g n a n c y . In v i e w of the possibility tl m a l i g n a n c y m a y d e p e n d on a gene dosage effect d e t e r m i n e d by the n u m b e r of cc ies of an a c t i v a t e d gene, c o m p a r e d w i t h t h o s e of a s u p p r e s s o r gene (perhaps t n o r m a l allele) on the h o m o l o g o u s c h r o m o s o m e , and in the light of e v i d e n c e t| h o m o z y g o s i t y or h e m i z y g o s i t y for r e c e s s i v e genes m a y be an i m p o r t a n t charact, istic of the cells of at least s o m e t u m o r s [82[, it is of interest to d e t e r m i n e from t s t u d y of h e t e r o c h r o m a t i n and e n z y m e p o l y m o r p h i s m s w h e t h e r , for instance, t aberrant and n o r m a l c h r o m o s o m e s #1 are d e r i v e d from the s a m e or different hon logs and w h e t h e r or not there is e v i d e n c e for the o c c u r r e n c e of s o m a t i c crossingo~ b e t w e e n the h o m o l o g s , as has been f o u n d for c h r o m o s o m e # 1 3 in cell lines deriv from testicular t u m o r s [831 and in r e t i n o b l a s t o m a s [84[. In c o n c l u s i o n , it s e e m s that c h r o m o s o m e #1 structural c h a n g e s are c o m m o n most, and probably all, forms of cancer, that t h e y o c c u r r e l a t i v e l y late in the coul of d e v e l o p m e n t of the n e o p l a s t i c stem line (although they m a y be p r e s e n t at i stage of, 0I" p r e c e d e , c o m m e n c i n g stromal i n v a s i o n l , and that a l t h o u g h it is possil that d u p l i c a t i o n of a g e n e or genes on the long arm is the significant event, in least s o m e types of n e o p l a s i a , breakage or loss i n v o l v i n g the short arm (in neu b l a s t o m a [1]) or specific t r a n s l o c a t i o n s (in l e u k e m i a s anti related disorders) are a important. 1 thank Miss Marion C. Baker for critically reading the manuscript and Mrs. B. I. Laogdon secretarial services.
REFERENCES 1. Gilbert F, Feder M, Balaban G, Brangman D, Lurie OK, Podolsky R, Rinaldt V. Vinikq N, Weisband I (1984): ttuman neuroblastomas and abnormalities of chromosomes 1 a 17. Cancer Res 44:5444-5449. 2. Atkin NB, Baker MC (1977): Abnormal chromosomes and number 1 heterochromatin ,, iants revealed in C-banded preparations from 13 bladder carcinomas. Cytobios 18:1t 109.
3. Atkin NB, Baker ME: (1985): Cytogenetic study of ten carcinomas of the bladder: lnvol ment of chromosomes 1 and 11. Cancer Genet Cytogenet 15:253-268. 4. Ayraud N, Lambert IC, Hufferman-Tribollei K, Basteris B (1977): A comparative cyte uetic study of seven carcinomas of mammary origin. Ann Genet 20:171-177. 5. Kovacs G (1978): Abnormalities of chromosome No. 1 in human solid malignant tumor Int J Cancer 21:688-694. 6. Pathak S (19801: Cytogenetic analysis in human breast tumors. Cancer Genet Cytoge 1:281-289. 7. Rodgers CS, Hill SM, Hult~n MA (1984): Cytogenetic analysis in human breast carcinol 1. Nine cases in the diploid range investigated using direct preparations. Cancer Ge Cytogenet 13:95-119. 8. Wurster-Hill Dtl, Maurer LH (1978): Cytogenetic diagnosis of cancer: Abnormalitie., chromosomes and polyploid levels in the bone marrow of patients with small cell a plastic carcinoma of the lung. J Nail ('ancer Inst 61:1065-1075. 9. Atkin NB, Baker MC (1979): Chrolnosome 1 in 26 carcinomas of the cervix uteri. Stl rural and numerical changes. Cancer 44:604-613. 10. Atkin NB, Baker MC (1982): Nonrandom chromosome changes in carcinoma of the cel uteri. I. Nine near-diploid tumors. Cancer Genet Cytogenet 7:209--222. 11. Atkin NB, Baker MC (1984): Nonrandom chromosome changes in carcinoma of the cel uteri. 11. Ten tumors in the triploid--tetraploid range. Cancer Genet Cylogenet 13:189-~
~1 A b e r r a t i o n s in C a n c e r
283
12. Kiricuta l, Suciu St, Giurgiuman M (1982): Chromosomenver~inderungen bei 20 L~isionen der Cervix uteri. Arch Geschwulstforsch 52:205-211. 13. Reichmann A, Martin P, Levin B (1984): Chromosomes in human large bowel tumors. A study of chromosome 1. Cancer Genet Cytogenet 12:295-301. 14. Douglass EC, Green AA, ttayes FA, Etcubanas E, Horowitz M, Wilimas J (1984): Chromosome 1 abnormalities: A common feature of pediatric solid tumors. Proc Annu Meet Am Assoc Cancer Res 25:37. 15. Douglass EC, Wilimas JA, Green AA, Look AT (1985}: Abnormalities of chromosomes 1 and 11 in Wilms' tumor. Cancer Genet Cytogenet 14:331-338. 16. Slater RM, de Kraker J, Voute PA, Delemarre JFM {1985): A cytogenetic study of Wilms' tumor. Cancer Genet Cytogenet 14:95-109. 17. Kaneko Y, Kondo K, Rowley JD, Moehr JW, Maurer HS (1983): Further chromosome studies on Wilms' tumor cells of patients without aniridia. Cancer Genet Cytogenet 10:191197. 18. Kondo K, Chilcote RR, Maurer HS, Rowley JD (1984): Chromosome abnormalities in tumor cells from patients with sporadic Wilms' tumor. Cancer Res 44:5376-5381. 19. Rowley JD (1977): Mapping of human chromosomal regions related to neoplasia: Evidence from chromosomes 1 and 17. Proc Natl Acad Sci USA 74:5729-5733. 20. Spriggs At, Holt JM, Bedford J (1976): Duplication of part of the long arm of chromosome 1 in marrow cells of a treated case of myelomatosis. Blood 48:595-599. 21. Papenhausen PR, Wolkin-Friedman E, Pekzar-Wissner C (1984): Novel tandem triplication of l q in a patient with a myelodysplastic syndrome. Cancer Genet Cytogenet 12:145-150. 22. Knuutila S, Ruutu T, Partanen S, Vuopio P (1983): Chromosome l q + in erythroid and granulocyte-monocyte precursors in a patient with essential thrombocythemia. Cancer Genet Cytogenet 9:245-249. 23. Morris CM, Fitzgerald PH, Neville MA, Wyld PJ, Beard MEJ (1984): Does multisomy of chromosome lq confer a proliferative advantage in B-cell acute lymphoblastic leukemia? Cancer 54:48-53. 24. Schmid E, K6hler J (1984): Involvement of chromosomes 1 and 11 in three cases with myeloproliferative diseases. Cancer Genet Cytogenet 11:121-123. 25. Slater RM, Philip P, Badsberg E, Behrendt H, Hansen NE, Van Heerde P (1979): A 14q + chromosome in a B-cell acute lymphocytic leukemia and in a case of leukemic non-endemic Burkitt lymphoma. Int ] Cancer 23:639--647. 26. Bauchinger M {1984): Trisomy lq and loss of Y chromosome in a male with osteomyelosclerosis. Acta Haematol 72:131-134. 27. Alimena G, Dallapiccola B, Mitelman F, Montuoro A (1980): Aberrations of chromosome No. 1 in blastic phase of chronic myeloid leukemia. Hereditas 92:59-63. 28. Geraedts JPM, Den Ottolander GJ, Ploem JE, Muntinghe OG (1980): An identical translocation between chromosome 1 and 7 in three patients with myelofibrosis and myeloid metaplasia. Br J Haematol 44:569-575. 29. Tomiyasu T, Sasaki M (1981): Atypical myelofibrosis associated with a partial duplication of the long arm of chromosome 1. Chromosome Information Service No. 31, pp 35-36. 30. Pasquali F, Francesconi D, Casalone R, lppoliti G (1979): Partial trisomy 1 due to 1/17 translocation in Phi-positive chronic myelocytic leukemia. Hum Genet 49:277-282. 31. Miyamoto K, Hamasaki K, Kitajima K, Adachi T, Tanaka T, Sato J (1981): Abnormalities of chromosome No. I related to blood dyscrasias: Study of 10 cases. Acta Med Okayama 35:137-141. 32. Mamaeva SE, Mamaev NN, Jartseva NM, Belyaeva LV, Scherbakova EG (1983): Complete or partial trisomy for the long arm of chromosome 1 in patients with various hematologic malignancies. Hum Genet 63:107-112. 33. Hossfeld DK, Schmidt CG (1978): Chromosome findings in effusions from patients with Hodgkin's disease. Int J Cancer 21:147-156. 34. Whang-Peng J, Bunn PA Jr, Knutsen T, Matthews MJ, Schechter G, Minna JD (1982): Clinical implications of cytogenetic studies in cutaneous T-cell lymphoma (CTC!,) Cancer 50:1539-1553. 35. Whang-Peng J, Lee EC, Sieverts H, Magrath IT (1984): Burkitt~s lymphoma in AIDS: Cytogenetic study. Blood 63:818.-822.
284
N . B . Atl
36. Panani A, Ferti-Passantonopoulou A, Dervenoulas J (1984): Partial duplication of lq i malignant lymphoma. Cancer Genet Cytogenet 11:87-90. 37. Slavutsky 1, Labal de Vinuesa M, Dupnnt J, Mondini N, Brieux de Salum S (1981): Abn malities of chromosome No. 1: Two cases with lymphocytic Iymphomas. Cancer Ge Cytogenet 3:341-346. 38. Kaneko K, Variakojis D, Kluskens L, Rowley JD (1982): Lymphoblastic lymphoma: C~ genetic, pathologic, and immunologic studies, lnl J Cancer 30:273-279. 39. Fukuhara S, Rowley JD, Variakojis D, Golomb HM (1979): Chromosome abnormalities poorly differentiated lymphocytic lymphoma. Cancer Res 39:3119-3128. 40. Rowley JD, Fukuhara S (1980): Chromosome studies in non-Hodgkin's lymphomas. Se~ Oncol 7:255-266. 41. G6dde-Salz E, Schwarze EW, Stein H, Lennert K, Grote W (1981): Cytogenetic findings T-zone lymphoma. J Cancer Res Clin Oncol 101:81-89. 42. Gaunt KL (1981): Non-random chromosome involvement in non-Burkitt, non-HodgJ lymphoma. Br J Cancer 44:930. 43. Mark J, Ekedahl C, Dahlenfors R (1978): Characteristics of the banding patterns in n~ Hodgkin and non-Burkitt lymphomas. Hereditas 88:229-242. 44. Miyamoto K, Miyano K, Miyoshi I, Hamasaki K, Nishihara R, Terao S, Kimura I, Ma~ K, Matsumura K, Nishijima K, Tanaka T (1980): Chromosome 14q + in a Japanese pati~ with Burkitt's lymphoma. Acta Med Okayama 34:61-65. 45. Douglass EC, Magrath IT, Lee EC, Whang-Peng J (1980]: Cytogenetic studies in non-A can Burkitt lymphoma. Blood 55:148-155. 46. Yunis JJ, Oken MM. Theologides A, Howe RB, Kaplan ME (1984}: Recurrent chromosot defects are found in most patients with non-Hodgkin's lymphoma. Cancer Genet Cyto net 13:17-28. 47. Becher R, Gibas Z, Karakousis C, Sandberg AA (1983): Nonrandom chromosome char in malignant melanoma. Cancer Res 43:5010-5016. 48. Balaban G, Herlyn M, Guerry D IV, Bartolo R, Koprowski H, Clark WH, Nowell PC {19~ Cytogenetics of h u m a n malignant melanoma and premalignant lesions. Cancer Genet I togenet 11:429-439. 49. Sandberg AA (1980}: The Chromosomes in Human Cancer and l.eukemia. Elsevier No Holland, New York. 50. Vermaelen K, Story P, Bosly A, Vail den Berghe H (1983): Translocation t(6:9) in a c of multiple myeloma. Ann Genet 26:56-57. 51. Liang W, Hopper JE, Rowley JD (1979): Karyotype abnormalities and clinical aspect~ patients with multiple myeloma and related paraproteinemic disorders. Cancer 44:6: 644. 52. Wurster-Hill DH, Mclntyre OR, Cornwell GG III (1978): Chromosome studies in myelt atosis. Virchows Arch B Cell Pathol 29:93-97. 53. Lewis JP, MacKenzie MR (1984): Multiple myeloma is associated with nonrandom c/~ mosomal abnormalities. Proc Annu Meet Am Soc Clin Oncol 3:9. 54. Gilbert F, Balaban G, Moorhead P, Bianchi D. Schlesinger H (1982): Abnormalities of c| mosome l p in h u m a n neuroblastoma tumors and cell lines. Cancer Genet Cytogenet 7:: 42. 55. Brodeur GM, Green AA, Hayes FA, Williams KJ, Williams DL, Tsiatis AA (1981): Cyic netic features of h u m a n neuroblastomas and cell lines. Cancer Res 41:4678-4686. 56. Atkin NB, Pickthall VJ (1977): Chromosomes 1 in 14 ovarian cancers. Heterochrom~ variants and structural changes. Hum Genet 38:25-33. 57. Whang-Peng J, Knutsen T, Douglass EC, Chu E, Ozols RF, Hogan WM, Young RC (19~ Cytogenetic studies in ovarian cancer. Cancer Genet Cytogenet 11:91-106. 58. Van der Riet-Fox MF, Retie[ AE, Van Niekerk WA (1979}: Chromosome changes in h u m a n neoplasms studied with banding. Cancer 44:2108-2119. 59. Atkin NB, Baker MC (1985}: Chromosome 10 deletions in carcinoma of the prostate Engl J Med 312:315. 60. Atkin NB, Baker MC (1985}: Chromosome study of five cancers of the prostate. Ilum G~ 70:359-364.
#1 A b e r r a t i o n s in (~an(:er
285
61. Bc'm.'dict WF, Banerjc'e A. Mark C. Murphree AL (1983): Nonrandom chromosomal changes in untreated retinoblastomas. Cancer (.;enet Cytogenet 10:311--333. 62. Gardner HA. Gallie BL, Kl~ight LA, Phillips RA 11982): Multiple karyotypic changes in retinoblastoma tumor cells: Presence of normal chromosome No. 13 in most tumors. Cancer (;enet Cyt()gem.q 6:201 2 ! 1. 63. Chaum E. Ellsworth RM, Abramson I)H, Haik BG. Kitchin FD, Chaganti RSK (1984l: Cytogenetic analysis of retinoblastoma: Evidence for multifocal origin and in r i v e gene amplification. Cytogenetic Cel) (;enet 38:82-91. 64. Kusnetsova I,E, Prigogina EL. Pogosianz liE. Belkina HM (19821: Similar chromosomal abnormalities in several retinoblastomas, l lure Genet 61:201 -204. 65. Becher R, Wake N, Gibas Z, Ochi 1I. Sandberg AA [1984): (]hromosome changes in soft tissue sarcomas. Proc Annu Meet Am Assoc Cancer Res 25:36. 66, Trent JM. Meltzer PS, Thompson FH, Casper iT. Fogh )E [1984): Nonrandom chromosome alterations in rhabdomyosar(:oma (RMS/: Possible association with a ras-related oncogene. Proc Annu Meet Am Asset: Cancer Res 25:66. 67. Atkin Nil, Baker MC (1985): Chromostmle analysis of three seminontas. Cancer (;enet Cytoge.net 17:315- 323. 68. Michael PM, Garson OM. Calhm DI" (1!}85}: A review of the t(l;19] breakpoints in acute Iymphoc'~,tic leukemia. Cancer Genet Cytogent;t 17:79-8(}. 69. Moir DJ, ]ones PAE. Pearson I, Duncan IR, Cook P, Buckle VJ (19841: A new translacation, t(l:3)(p36;q21), in myelodysplastic disorders. Blood 64:553--555. 70. Scheres IMJC, Hustinx ']'Wl, IIoldrinet RS(.;, Geraedts JPM, Hagemeijer A, van der BlijPhilipsen M (1984): Translocation 1:7 in dyshematopoiesis: Possibly induced with a nonrandom geographit: distribution. Cancer Gem;t ('ytogenet 12:283--294. 71. Brito-Bahapulle V, Atkin NB (1981): Breakpoints in chromosome 1 abnormalities of 218 human neoplasms. Cancer (;enet Cytogenet 4:215-225. 72. Rowley JD [19751: Abnormalities of chromosr~me l in myeloproliferative disorders. Cancer 36:1748-1758. 73. Alimena G, Brandt L, Dallapiccola B, Mitehnan F, Nilsson PG (1979]: Secondary chromosome changes in chronic myeloid leukemia: Relation to treatment. Cancer Genet Cytogenet 1:79-85. 74. Atkin NB, Baker MC, Eerti-Passantonopoulou A (19831: Chrontosome changes in early gynecologic malignancies. At:ta Cytol 27:450-453. 75. Rahin M. Watson M. Barker PE, Ryan J, Breg WR. Ruddle 1.'I-t (19841: NRAS transforming gene maps to region p l l - - , p l 3 on chromosome 1 by in situ hybridization. Cytogenet Cell Genet 38:70-72. 76. Morton ('C. Taub R. Diamond A, Lane MA. Cooper (;M. Leder P (1984): Mapping of the human Blym-1 transforming gene activated in Burkitt lymphomas to chromosome 1. Science 223:173-175. 77. Le Beau MM, Westbrook CA. l)iaz MO, Rowley ID (19841: Evidence for two distinct c-src loci on human chromosomes 1 and 20. Nature 312:70-71. 78. Balazs I, Grzeschik KI'I, Stavnezer E (1984]: Assignment of the human homologue of a chicken oncogene to chromosome 1. Cytogenet Cell Genet 37:410-411. 79. Yunis JJ, Soreng AI, (19841: Constitutive fragile sites and cancer. Science 226:1199.-1204. 80. Benedict WE. Weissman BE. Mark C. Stanbridge El (1984): Tunmrigenicity of human ttT1080 fibrosarcoma X normal fibroblast hybrids: ('hromosome dosage dependency. Cancer Res 44:3471-3479. 81. Stoler A, Bouck N [1985): Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transl~ormation. Proc Natl Acad Sci USA 82:570-574. 82, Murphree AI,. Benedict WF (19841: Retinoblastoma: Clues to human oncogenesis. Science 223:1028-1(133. 83. Parrington JM, West LF [1985): Loss of chromosome and enzyme markers in cultures from testicular tumt~urs. Clin Genet 27:326 (ahstr}. 84. Cavenee WK, I)ryja TP, Phillips RA, Benedict WE, Godbout R, Gallic BL, Murphree AL, Strong LC, White RL [1983): Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779-784.