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What should oncologists know about cytogenetics in solid tumors?
Annals ofOncology 4: 821-824, 1993. © 1993 Kluwer Academic Publishers. Printed in the Netherlands.
Review What should oncologists know about cytogenetics in solid tumors? P. Dal Cin1 & J. M. Trent2'3 Departments of 2Radiation Oncology, and 3Human Genetics, The University of Michigan Medical Center, Ann Arbor, MI, U.S.A., 1 Centre for Human Genetics, University of Leuven, Leuven, Belgium
Despite the fact that gross chromosome changes in malignant tumors were first described in human solid tumors more than 100 years ago by Arnold [1], cytogenetic analysis of solid tumors is still in its infancy compared to studies of leukemic cells [for review see 2, 3]. Advances in solid tumor cytogenetics have been and still are at the mercy of methodology, with the most limiting factors being: 1) low mitotic index (necessitating short term culture of cancer cells to avoid overgrowth by normal stromal or supporting cells); 2) microbiably infected or necrotic samples (that results in destruction of cancer cells before culturing); and 3) the occurrence of multiple and complex chromosomal changes (which make it difficult to identify the primary chromosome change associated with a specific tumor type). Despite these problems, recent advances in cytogenetic techniques coupled to increasing cooperation between surgeons and pathologists to obtain appropriate tumor material, has resulted in the detailed examination of the karyotypes of a number of tumors with the same histology which in turn has led to the description of a number of specific chromosome changes in solid tumors (Table 1). The number of solid tumors cytogenetically characterized is still small, as well as the number of cases of chromosomally investigated tumors of each subtype. However, several conclusions can already be drawn regarding this area of research.
1. The concept that chromosome abnormalities are exclusively related to malignant cells clearly has to be revised.
A variety of specific chromosome changes have now been identified in several benign neoplasms (Table 1) and certain chromosome regions seem to be non-randomly affected. The most frequently altered areas include: 1) the 12ql3-ql5 region in typical lipomas, uterine leiomyomas, pleomorphic adenomas of salivary
gland and recently also in endometrial polyps [4]; 2) the terminal region of the short arm of chromosome 6 in lipomas, uterine leiomyomas and also in endometrial polyps [5]; 3) the 13ql2-q22 region in lipomas and uterine leiomyomas; 4) an extra chromosome 12 in uterine leiomyomas and benign ovarian tumors, i.e. fibroma, thecomas, and fibrothecomas [6]. By definition, the major difference between benign and malignant tumors is the ability of the latter to invade and metastasize. It appears likely that as additional insights are gained regarding the molecular changes underlying chromosome alterations, new insights into the progression of malignancy will arise.
2. Cytogenetic findings can be used today by the pathologist, and oncologist to assist in assigning the correct diagnosis of tumors lacking either a specific marker of cellular differentiation or displaying a characteristic histology.
A specific example of tumors in which cytogenetics may be useful are the childhood cancers, Ewing's sarcoma, neuroblastoma, and rhabdomyosarcoma, where correct diagnosis is difficult to achieve because of a virtually identical microscopic picture of the undifferentiated cells. Several new methods help in establishing ther correct diagnosis of these tumors, of which cytogenetics is one [7]. All these tumors demonstrate unique chromosomal changes A t(2;13)(q35-37;ql4) or its variant t(l;13)(p36;ql4) has been mainly associated with alveolar rhabdomyosarcoma [8, 9]. Neuroblastomas are characterized either by loss of the terminal region of the short arm of chromosome 1 (mainly Ip32-lp36) or by double minute chromosome or homogeneously staining regions (resulting from gene amplification of N-myc) [10]. A reciprocal translocation between chromosomes 11 and 22, t(ll;22)(q24; ql2) has been found in 92% of Ewing's sarcoma cases and also in peripheral neuroectodermal tumors [12].
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Key words: chromosomes, cancer
822 Table 1.
Chromosome changes'
Benign Meningioma Pleomorphic adenoma of the salivary gland Lipoma Leiomyoma (uterine) Colonic adenoma Endometrial polyp Follicular thyroid Cytadenomalymphoma (Warthin's tumor) Fibroma (ovary) Renal cell adenoma Oncocytoma
-22/22qt(3;8)(p21;ql2)/t with 12q 14-15 t with 12ql4/t with 6p22-23/13q-/+r t with 12ql4-15/7q-/+12/13q-/t(l;2)(p36;p34)/t with 6p22-23 12q-/+8 t with 6p22-23/t with 12ql4-15 t with 19ql3/t(2;3)q21;p24) t(ll;19)(q21;13) +12 -Y, +7,+7,+17 -Y,-1
Adenocarcinoma Bladder Prostate Lung (SCLC)b Colon Kidney Uterus Ovary Papillary thyroid
i(5p)/+7/-9or9q-/Hpdel(10)(q24) del(3)(pl4p23) 12q-7+77+87+12717(qll) c -18 C del(3)(pll-p21)/t(x;l)(pll.2;q21.1)
10qll-tq26
Sarcoma Liposarcoma (myxoid) Synovia] sarcoma Rabdomyosarcoma (alveolar) Extraskeletal myxoid chondrosarcoma Leiomyosarcoma (small bowel) Fibrosarcoma (congenital) Dermatofibrosarcoma protuberans Endometrial stromal sarcoma Clear cell sarcoma
t(12;16)(ql3;pll) t(X;18)(pll.2;qll.2) t(2;13)(q37;ql4)/t(l;13)(p36;ql4) t(9;22)(q31;ql2.2) t or del(l)(pl2-13) combination of trisomiesc +r t(7;17)(pl5-21;ql2-21) t(12;22)(ql3;ql2)
Embryonal and other Germ cell tumors (gonadal and extragonadal) Retinoblastoma Wilms' tumor Neuroblastoma Medulloblastoma Malignant melanoma Mesothelioma Ewing's sarcoma, PNET b
i(12p) del(13)(ql4)d/i(6p)c del(ll)(pl3) d del(l)(p32p36) i(17q) del(6Xqllq27)7i(6p)7del(l)(pllp22)7t(119)(ql2;ql3) del(3)(pl3-p23) t(ll;22)(q24;ql2)
* divides subgroups in the same entity; b SCLC: small cell lung cancer; PNET: peripheral neuroendocrine tumor; c not yet proven to be primary; d associated with a constitutional chromosome change.
3. A number of different are being recognized 'unique' tumor entity, a biologically different
primary cytogenetic changes within a histopathologically each possibly characterizing subtype.
For example, transitional cell carcinoma of the bladder histologically appears to be a rather uniform tumor. CytogeneticaLly, it has been possible to define several subgroups, each characterized by a specific chromosome change such as i(5p) or 5q—, +7, - 9 or 9q—, Up— [13]. At least 7 cytogenetically distinct subgroups have been described in uterine leiomyoma; those with involvement of 12ql4-15, 6p21-pter those with 7q-, 13q—, those with t(l;2), trisomy 12 and those with a normal karyotype [14]. Histologically these subgroups are indistinguishable, as is the case in lipoma-sub-
groups [15]. These findings may suggest that each subgroup may ultimately correlate with specific parameters such as course of the disease, stage an grade of the cancer, anatomic site of the tumor, biological behavior, response to therapy or to hormones, recurrence, survival, etc. 4. An identical chromosome abnormality may be observed in a tumor derived from cells of the same lineage but a different level of differentiation.
The occurrence of one or more copies of an isochromosome of the short arm of chromosome 12, i(12p), is striking and apparently characteristic of 80% of the germ cell tumors (GCTs) not only of the testis, but also in ovarian and extragonadal GCTs. This finding sug-
Downloaded from https://academic.oup.com/annonc/article-abstract/4/10/821/178154 by guest on 19 January 2019
Tumors
823 gests that through an unknown mechanism of a specific chromosome change may occur in an undifferentiated gonocyte [16]. The t(ll;22)(q24;ql2) originally described in Ewing's sarcoma, was also found in peripheral neuroectodermal tumors (PNTs) [17], Askin tumor [18], esthesioneuroblastoma [19], neuroendocrine tumor of the small intestine [20], and extraskeletal Ewing's sarcoma [21]. These cytogenetic findings provide support for a common neuroectodermaJ origin of all these malignancies [22].
The exact role of chromosome abnormalities in human cancers clearly requires additional study. However, there is significant information now implicating cytogenetic rearrangements as early and perhaps causative changes in some human cancers. Of clinical relevance, information which is continuing to accrue in both hematologic and more recently solid tumors provides evidence that clinically useful information will indeed be forthcoming. We believe that with the continued focus on cytogenetic analysis of solid tumors (coupled with the tremendous emphasis now on fluorescence in situ hybridization) new karyotypic information will be forthcoming and is likely to be of distinct value to clinical oncologists.
References A specific translocation between chromosomes X and 18 t(X;18)(pll.2;qll.2) characterizes synovial sarcoma, primary or recurrent or metastasis, whatever the histologic pattern, i.e. biphasic, monophasic or poorly differentiated [23]. A t(12;16)(ql3;pll) has been found to be restricted to myxoid liposarcoma whereas long marker, ring(s) occur in well-differentiated liposarcoma [24]. Clear cell sarcomas, also known as 'melanoma of the soft parts' have recently been characterized by a t(12;22)(ql3;ql2)[25]. Table 1 provides further information illustrating this remarkable specificity of chromosome change in sarcomas. Importantly, several genes have been recently identified at the sites of chromosomal alterations in sarcomas [for review see 3]. 6. Clinical correlation's of chromosome change is of unquestioned value in prognosticating hematopoietic malignancies. Clinical correlation's of solid tumors is in its infancy, but likely will prove of similar value. Although the value of chromosome analysis has been well established in hematologic malignancies, the relationship between chromosome abnormalities and clinical outcome in most solid tumors has received little study. Nevertheless, several recent studies have provided preliminary information of the relationship of cytogenetic abnormalities and clinical outcome in solid tumors [26, 27]. Because there is a large number of comparisons necessitated by the design of these studies (e.g., comparison of clinical parameters with multiple chromosome rearrangements), the general significance of these results are still unclear and require further corroboration. However, based upon the clinical utility of the blood-borne cancers of man, it seems likely that analysis of solid tumors will prove to be of similar clinical value.
1. Arnold J. Beobachtungen uber Kemteilungen in den Zellen der Geschwulste. Virchow's Arch pathol Anat 1879b; 78: 270-301. 2. Trent JM, Meltzer PS. The last shall be first. Nature Genetics 1993; 3: 101-2. 3. Sandberg AA. The Chromosomes in Human Cancer and Leukemia, 2nd Edition. New York, Elsevier North-Holland, Inc., 1990. 4. Vanni R, Dal Cin P, Marras S et al. Endometrial polyp: Another benign tumor characterized by 12ql3-15 changes. Cancer Genet Cytogenet 1993; in press. 5. Dal Cin P, De Wolf F, Klerckx P et al. The 6p21 chromosome region is non randomly involved in endometrial polyps. Gynecol Oncol 1992; 46: 393-6. 6. Sreekantaiah C, Sandberg AA. Clustering of aberrations to specific chromosome regions in benign neoplasms. Int J Cancer 1991; 48: 194-8. 7. Donner LR. Cytogenetics and molecular biology of small round-cell tumors and related neoplasms. Current status. Cancer Genet Cytogenet 1991; 54:1-10. 8. Douglass EC, Valentine M, Etcubanas E et al. A specific chromosomal abnormality in rhabdomyosarcoma. Cytogenet Cell Genet 1987; 45:148-55. 9. Dal Cin P, Brock P, Aly MS et al. A variant 2; 13 translocation in rhabdomyosarcoma. Cancer Genet Cytogenet 1991; 55: 191-5. 10. Brodeur GM, Fong C. Molecular biology and genetics of human neuroblastoma. Cancer Genet Cytogenet 1989; 41: 153-74. 11. Turc-Carel C, Aurias A, Mugneret F et al. Chomosomes in Ewing's sarcoma. I. An evaluation of 85 cases and remarkable consistency of t(ll;22)(q24;ql2). Cancer Genet Cytogenet 1988; 32:229-38. 12. Douglass EC, Rowe ST, Valentine M et al. A second nonrandom translocation, der(16)t(l; 16)(q21 ;ql3), in Ewing sarcoma and peripheral neuroectodermal tumor. Cytogenet Cell Genet 1990; 53: 87-90. 13. Sandberg AA. Chromosome changes in bladder cancer Clinical and other correlations. Cancer Genet Cytogenet 1986; 19: 163-75. 14. Nilbert M, Heim S. Uterine leiomyoma cytogenetics. Genes Chrom Cancer 1990; 2: 3-13. 15. Sreekantaiah C, Leong SPL, Karakousis CP et al. Cytogenetic profile of 109 lipomas. Cancer Res 1991; 51:422-33. 16. de Jong B, Oosterhuis JW, Castedo SMMJ et al. Pathogenesis of adult testicular germ cell tumors. A cytogenetic model. Cancer Genet Cytogenet 1990; 48:143-67.
Downloaded from https://academic.oup.com/annonc/article-abstract/4/10/821/178154 by guest on 19 January 2019
5. Of all solid tumors, sarcomas have the highest degree of specificity of chromosome alteration since they are associated with defined rranslocations specific to each histopathologically recognizable tumor subtype.
7. Summary and future perspectives
824 changes in soft-tissue sarcomas. Archives of Surgery 1987; 122:1257-60. 25. Fletcher JA. Translocation t(12;22)(ql3-14;ql2) is a nonrandom aberration in soft-tissue clear-cell sarcoma. Genes Chrom Cancer 1992; 5: 184. 26. Trent JM, Meyskens FL, Salmon SE et al. Relation of cytogenetic abnormalities and clinical outcome in metastau'c melanoma. New England Journal of Medicine 1990; 322:1508-11. 27. Rodriguez E, Mathew S, Reuter VE et al. Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors. Cancer Res 1992; 52: 2285-91. Received 23 March 1993; accepted 25 March 1993. Correspondence to: Jeffrey M. Trent, Ph.D. Departments of Radiation Oncology and Human Genetics The University of Michigan Medical School MSRBIIC560 1150 West Medical Center Drive Ann Arbor, Michigan 48109-0668, USA.
Downloaded from https://academic.oup.com/annonc/article-abstract/4/10/821/178154 by guest on 19 January 2019
17. Whang-Peng J, Triche TJ, Knutsen T et al. Chromosome translocation in peripheral neuroepithelioma. New Engl J Med 1984; 311: 584-5. 18. De Chadarevlan JP, Vekemans M, Seemayer TA. Reciprocal translocation in small-cell sarcomas. New Engl J Med 1984; 311: 1702-3. 19. Whang-Peng J, Freter CE, Knutsen T et al. Translocation t(ll;22) in estesioneuroblastoma. Cancer Genet Cytogenet 1987; 29:155-7. 20. Vigfusson NV, Allen LJ, Phillips JH et al. A neuroendocrine tumor of the small intesine with karyotype of 46,XY,t(ll;22). Cancer Genet Cytogenet 1986; 22:211-8. 21. Becroft DMO, Pearson A, Shaw RE et al. Chromosome translocation in extraskeletal Ewing's tumour. Lancet 1984; 2:400. 22. Lizard-Nacol S, Lizard G, Justrabo E et al. Immunologic characterization of Ewing's sarcoma using mesenchymal and neural markers. AmJPathol 1989; 135: 847-55. 23. Dal Cin P, Rao U, Janl-Sait S et al. Chromosomes in the diagnosis of sort tissue tumors. I. Synovial sarcoma. Modern Pathol 1992; 6: 357-62. 24. Karakousis CP, Dal Cin P, Turc-Carel C et al. Chromosomal
Review What should oncologists know about cytogenetics in solid tumors? P. Dal Cin1 & J. M. Trent2'3 Departments of 2Radiation Oncology, and 3Human Genetics, The University of Michigan Medical Center, Ann Arbor, MI, U.S.A., 1 Centre for Human Genetics, University of Leuven, Leuven, Belgium
Despite the fact that gross chromosome changes in malignant tumors were first described in human solid tumors more than 100 years ago by Arnold [1], cytogenetic analysis of solid tumors is still in its infancy compared to studies of leukemic cells [for review see 2, 3]. Advances in solid tumor cytogenetics have been and still are at the mercy of methodology, with the most limiting factors being: 1) low mitotic index (necessitating short term culture of cancer cells to avoid overgrowth by normal stromal or supporting cells); 2) microbiably infected or necrotic samples (that results in destruction of cancer cells before culturing); and 3) the occurrence of multiple and complex chromosomal changes (which make it difficult to identify the primary chromosome change associated with a specific tumor type). Despite these problems, recent advances in cytogenetic techniques coupled to increasing cooperation between surgeons and pathologists to obtain appropriate tumor material, has resulted in the detailed examination of the karyotypes of a number of tumors with the same histology which in turn has led to the description of a number of specific chromosome changes in solid tumors (Table 1). The number of solid tumors cytogenetically characterized is still small, as well as the number of cases of chromosomally investigated tumors of each subtype. However, several conclusions can already be drawn regarding this area of research.
1. The concept that chromosome abnormalities are exclusively related to malignant cells clearly has to be revised.
A variety of specific chromosome changes have now been identified in several benign neoplasms (Table 1) and certain chromosome regions seem to be non-randomly affected. The most frequently altered areas include: 1) the 12ql3-ql5 region in typical lipomas, uterine leiomyomas, pleomorphic adenomas of salivary
gland and recently also in endometrial polyps [4]; 2) the terminal region of the short arm of chromosome 6 in lipomas, uterine leiomyomas and also in endometrial polyps [5]; 3) the 13ql2-q22 region in lipomas and uterine leiomyomas; 4) an extra chromosome 12 in uterine leiomyomas and benign ovarian tumors, i.e. fibroma, thecomas, and fibrothecomas [6]. By definition, the major difference between benign and malignant tumors is the ability of the latter to invade and metastasize. It appears likely that as additional insights are gained regarding the molecular changes underlying chromosome alterations, new insights into the progression of malignancy will arise.
2. Cytogenetic findings can be used today by the pathologist, and oncologist to assist in assigning the correct diagnosis of tumors lacking either a specific marker of cellular differentiation or displaying a characteristic histology.
A specific example of tumors in which cytogenetics may be useful are the childhood cancers, Ewing's sarcoma, neuroblastoma, and rhabdomyosarcoma, where correct diagnosis is difficult to achieve because of a virtually identical microscopic picture of the undifferentiated cells. Several new methods help in establishing ther correct diagnosis of these tumors, of which cytogenetics is one [7]. All these tumors demonstrate unique chromosomal changes A t(2;13)(q35-37;ql4) or its variant t(l;13)(p36;ql4) has been mainly associated with alveolar rhabdomyosarcoma [8, 9]. Neuroblastomas are characterized either by loss of the terminal region of the short arm of chromosome 1 (mainly Ip32-lp36) or by double minute chromosome or homogeneously staining regions (resulting from gene amplification of N-myc) [10]. A reciprocal translocation between chromosomes 11 and 22, t(ll;22)(q24; ql2) has been found in 92% of Ewing's sarcoma cases and also in peripheral neuroectodermal tumors [12].
Downloaded from https://academic.oup.com/annonc/article-abstract/4/10/821/178154 by guest on 19 January 2019
Key words: chromosomes, cancer
822 Table 1.
Chromosome changes'
Benign Meningioma Pleomorphic adenoma of the salivary gland Lipoma Leiomyoma (uterine) Colonic adenoma Endometrial polyp Follicular thyroid Cytadenomalymphoma (Warthin's tumor) Fibroma (ovary) Renal cell adenoma Oncocytoma
-22/22qt(3;8)(p21;ql2)/t with 12q 14-15 t with 12ql4/t with 6p22-23/13q-/+r t with 12ql4-15/7q-/+12/13q-/t(l;2)(p36;p34)/t with 6p22-23 12q-/+8 t with 6p22-23/t with 12ql4-15 t with 19ql3/t(2;3)q21;p24) t(ll;19)(q21;13) +12 -Y, +7,+7,+17 -Y,-1
Adenocarcinoma Bladder Prostate Lung (SCLC)b Colon Kidney Uterus Ovary Papillary thyroid
i(5p)/+7/-9or9q-/Hpdel(10)(q24) del(3)(pl4p23) 12q-7+77+87+12717(qll) c -18 C del(3)(pll-p21)/t(x;l)(pll.2;q21.1)
10qll-tq26
Sarcoma Liposarcoma (myxoid) Synovia] sarcoma Rabdomyosarcoma (alveolar) Extraskeletal myxoid chondrosarcoma Leiomyosarcoma (small bowel) Fibrosarcoma (congenital) Dermatofibrosarcoma protuberans Endometrial stromal sarcoma Clear cell sarcoma
t(12;16)(ql3;pll) t(X;18)(pll.2;qll.2) t(2;13)(q37;ql4)/t(l;13)(p36;ql4) t(9;22)(q31;ql2.2) t or del(l)(pl2-13) combination of trisomiesc +r t(7;17)(pl5-21;ql2-21) t(12;22)(ql3;ql2)
Embryonal and other Germ cell tumors (gonadal and extragonadal) Retinoblastoma Wilms' tumor Neuroblastoma Medulloblastoma Malignant melanoma Mesothelioma Ewing's sarcoma, PNET b
i(12p) del(13)(ql4)d/i(6p)c del(ll)(pl3) d del(l)(p32p36) i(17q) del(6Xqllq27)7i(6p)7del(l)(pllp22)7t(119)(ql2;ql3) del(3)(pl3-p23) t(ll;22)(q24;ql2)
* divides subgroups in the same entity; b SCLC: small cell lung cancer; PNET: peripheral neuroendocrine tumor; c not yet proven to be primary; d associated with a constitutional chromosome change.
3. A number of different are being recognized 'unique' tumor entity, a biologically different
primary cytogenetic changes within a histopathologically each possibly characterizing subtype.
For example, transitional cell carcinoma of the bladder histologically appears to be a rather uniform tumor. CytogeneticaLly, it has been possible to define several subgroups, each characterized by a specific chromosome change such as i(5p) or 5q—, +7, - 9 or 9q—, Up— [13]. At least 7 cytogenetically distinct subgroups have been described in uterine leiomyoma; those with involvement of 12ql4-15, 6p21-pter those with 7q-, 13q—, those with t(l;2), trisomy 12 and those with a normal karyotype [14]. Histologically these subgroups are indistinguishable, as is the case in lipoma-sub-
groups [15]. These findings may suggest that each subgroup may ultimately correlate with specific parameters such as course of the disease, stage an grade of the cancer, anatomic site of the tumor, biological behavior, response to therapy or to hormones, recurrence, survival, etc. 4. An identical chromosome abnormality may be observed in a tumor derived from cells of the same lineage but a different level of differentiation.
The occurrence of one or more copies of an isochromosome of the short arm of chromosome 12, i(12p), is striking and apparently characteristic of 80% of the germ cell tumors (GCTs) not only of the testis, but also in ovarian and extragonadal GCTs. This finding sug-
Downloaded from https://academic.oup.com/annonc/article-abstract/4/10/821/178154 by guest on 19 January 2019
Tumors
823 gests that through an unknown mechanism of a specific chromosome change may occur in an undifferentiated gonocyte [16]. The t(ll;22)(q24;ql2) originally described in Ewing's sarcoma, was also found in peripheral neuroectodermal tumors (PNTs) [17], Askin tumor [18], esthesioneuroblastoma [19], neuroendocrine tumor of the small intestine [20], and extraskeletal Ewing's sarcoma [21]. These cytogenetic findings provide support for a common neuroectodermaJ origin of all these malignancies [22].
The exact role of chromosome abnormalities in human cancers clearly requires additional study. However, there is significant information now implicating cytogenetic rearrangements as early and perhaps causative changes in some human cancers. Of clinical relevance, information which is continuing to accrue in both hematologic and more recently solid tumors provides evidence that clinically useful information will indeed be forthcoming. We believe that with the continued focus on cytogenetic analysis of solid tumors (coupled with the tremendous emphasis now on fluorescence in situ hybridization) new karyotypic information will be forthcoming and is likely to be of distinct value to clinical oncologists.
References A specific translocation between chromosomes X and 18 t(X;18)(pll.2;qll.2) characterizes synovial sarcoma, primary or recurrent or metastasis, whatever the histologic pattern, i.e. biphasic, monophasic or poorly differentiated [23]. A t(12;16)(ql3;pll) has been found to be restricted to myxoid liposarcoma whereas long marker, ring(s) occur in well-differentiated liposarcoma [24]. Clear cell sarcomas, also known as 'melanoma of the soft parts' have recently been characterized by a t(12;22)(ql3;ql2)[25]. Table 1 provides further information illustrating this remarkable specificity of chromosome change in sarcomas. Importantly, several genes have been recently identified at the sites of chromosomal alterations in sarcomas [for review see 3]. 6. Clinical correlation's of chromosome change is of unquestioned value in prognosticating hematopoietic malignancies. Clinical correlation's of solid tumors is in its infancy, but likely will prove of similar value. Although the value of chromosome analysis has been well established in hematologic malignancies, the relationship between chromosome abnormalities and clinical outcome in most solid tumors has received little study. Nevertheless, several recent studies have provided preliminary information of the relationship of cytogenetic abnormalities and clinical outcome in solid tumors [26, 27]. Because there is a large number of comparisons necessitated by the design of these studies (e.g., comparison of clinical parameters with multiple chromosome rearrangements), the general significance of these results are still unclear and require further corroboration. However, based upon the clinical utility of the blood-borne cancers of man, it seems likely that analysis of solid tumors will prove to be of similar clinical value.
1. Arnold J. Beobachtungen uber Kemteilungen in den Zellen der Geschwulste. Virchow's Arch pathol Anat 1879b; 78: 270-301. 2. Trent JM, Meltzer PS. The last shall be first. Nature Genetics 1993; 3: 101-2. 3. Sandberg AA. The Chromosomes in Human Cancer and Leukemia, 2nd Edition. New York, Elsevier North-Holland, Inc., 1990. 4. Vanni R, Dal Cin P, Marras S et al. Endometrial polyp: Another benign tumor characterized by 12ql3-15 changes. Cancer Genet Cytogenet 1993; in press. 5. Dal Cin P, De Wolf F, Klerckx P et al. The 6p21 chromosome region is non randomly involved in endometrial polyps. Gynecol Oncol 1992; 46: 393-6. 6. Sreekantaiah C, Sandberg AA. Clustering of aberrations to specific chromosome regions in benign neoplasms. Int J Cancer 1991; 48: 194-8. 7. Donner LR. Cytogenetics and molecular biology of small round-cell tumors and related neoplasms. Current status. Cancer Genet Cytogenet 1991; 54:1-10. 8. Douglass EC, Valentine M, Etcubanas E et al. A specific chromosomal abnormality in rhabdomyosarcoma. Cytogenet Cell Genet 1987; 45:148-55. 9. Dal Cin P, Brock P, Aly MS et al. A variant 2; 13 translocation in rhabdomyosarcoma. Cancer Genet Cytogenet 1991; 55: 191-5. 10. Brodeur GM, Fong C. Molecular biology and genetics of human neuroblastoma. Cancer Genet Cytogenet 1989; 41: 153-74. 11. Turc-Carel C, Aurias A, Mugneret F et al. Chomosomes in Ewing's sarcoma. I. An evaluation of 85 cases and remarkable consistency of t(ll;22)(q24;ql2). Cancer Genet Cytogenet 1988; 32:229-38. 12. Douglass EC, Rowe ST, Valentine M et al. A second nonrandom translocation, der(16)t(l; 16)(q21 ;ql3), in Ewing sarcoma and peripheral neuroectodermal tumor. Cytogenet Cell Genet 1990; 53: 87-90. 13. Sandberg AA. Chromosome changes in bladder cancer Clinical and other correlations. Cancer Genet Cytogenet 1986; 19: 163-75. 14. Nilbert M, Heim S. Uterine leiomyoma cytogenetics. Genes Chrom Cancer 1990; 2: 3-13. 15. Sreekantaiah C, Leong SPL, Karakousis CP et al. Cytogenetic profile of 109 lipomas. Cancer Res 1991; 51:422-33. 16. de Jong B, Oosterhuis JW, Castedo SMMJ et al. Pathogenesis of adult testicular germ cell tumors. A cytogenetic model. Cancer Genet Cytogenet 1990; 48:143-67.
Downloaded from https://academic.oup.com/annonc/article-abstract/4/10/821/178154 by guest on 19 January 2019
5. Of all solid tumors, sarcomas have the highest degree of specificity of chromosome alteration since they are associated with defined rranslocations specific to each histopathologically recognizable tumor subtype.
7. Summary and future perspectives
824 changes in soft-tissue sarcomas. Archives of Surgery 1987; 122:1257-60. 25. Fletcher JA. Translocation t(12;22)(ql3-14;ql2) is a nonrandom aberration in soft-tissue clear-cell sarcoma. Genes Chrom Cancer 1992; 5: 184. 26. Trent JM, Meyskens FL, Salmon SE et al. Relation of cytogenetic abnormalities and clinical outcome in metastau'c melanoma. New England Journal of Medicine 1990; 322:1508-11. 27. Rodriguez E, Mathew S, Reuter VE et al. Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors. Cancer Res 1992; 52: 2285-91. Received 23 March 1993; accepted 25 March 1993. Correspondence to: Jeffrey M. Trent, Ph.D. Departments of Radiation Oncology and Human Genetics The University of Michigan Medical School MSRBIIC560 1150 West Medical Center Drive Ann Arbor, Michigan 48109-0668, USA.
Downloaded from https://academic.oup.com/annonc/article-abstract/4/10/821/178154 by guest on 19 January 2019
17. Whang-Peng J, Triche TJ, Knutsen T et al. Chromosome translocation in peripheral neuroepithelioma. New Engl J Med 1984; 311: 584-5. 18. De Chadarevlan JP, Vekemans M, Seemayer TA. Reciprocal translocation in small-cell sarcomas. New Engl J Med 1984; 311: 1702-3. 19. Whang-Peng J, Freter CE, Knutsen T et al. Translocation t(ll;22) in estesioneuroblastoma. Cancer Genet Cytogenet 1987; 29:155-7. 20. Vigfusson NV, Allen LJ, Phillips JH et al. A neuroendocrine tumor of the small intesine with karyotype of 46,XY,t(ll;22). Cancer Genet Cytogenet 1986; 22:211-8. 21. Becroft DMO, Pearson A, Shaw RE et al. Chromosome translocation in extraskeletal Ewing's tumour. Lancet 1984; 2:400. 22. Lizard-Nacol S, Lizard G, Justrabo E et al. Immunologic characterization of Ewing's sarcoma using mesenchymal and neural markers. AmJPathol 1989; 135: 847-55. 23. Dal Cin P, Rao U, Janl-Sait S et al. Chromosomes in the diagnosis of sort tissue tumors. I. Synovial sarcoma. Modern Pathol 1992; 6: 357-62. 24. Karakousis CP, Dal Cin P, Turc-Carel C et al. Chromosomal