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Interstitial deletion of chromosome 11q in a pineoblastoma
Interstitial Deletion of Chromosome 11q in a Pineoblastoma Chandrika Sreekantaiah, Hubert Jockin, Martin L. Brecher, and Avery A. Sandberg
ABSTRACT: A case of pineohlastama with an interesting c.vtogenetic abnormality is reported. ('hromosomal analysis rff cultured cells from the tumor of a lO-week-ald white mah: revealed an interstitial deletion of the long arm of chromosome 11, del(ll)lq13.1q13.51. Tumors o.f the pineal region are relatively rare, and this is the .first report of a pineoblastama with del(1 lqJ.
INTRODUCTION Primary tumors of the central nervous system (CNS) comprise 2 - 5 % of all neoplasms and account for approximately 2% of all cancer deaths [1]. In children, brain tumors are second only to leukemia and comprise the most c o m m o n group of solid tumors of the young constituting 20% of all pediatric neoplasms [2]. The pediatric brain tumors are known to differ significantly in histology and clinical behavior from those of adults [2]. Pineal tumors consist of a variety of tumors unified by their c o m m o n location and not by any histologic similarities. The pineoblastomas considered to be primitive neuroectodermal tumors are poorly differentiated, small-cell tumors derived from pineal glandular cells. Their occurrence is extremely rare. and they show a marked male p r e d o m i n a n c e [3]. A number of specific c h r o m o s o m e abnormalities have been described in CNS tumors and other neurogenic tumors, notably meningiomas [4-7], gliomas [8, 9], medulloblastomas [10], and neuroblastomas [11, 12]. Reports on the cytogenetics of pineoblastomas are scarce; only two cases having been reported [13]. We describe a 10-week-old male baby with pineoblastoma and deletion of 11q.
CASE REPORT The patient was presented to his pediatrician at 6 weeks of age for routine examination and was noted to have a large head with bulging fontanelle. A history of downward gaze for approximately 3 weeks and lack of other signs of increased intracranial
From tile Cytogenetics Laboratory {C. S.) anti Pediatrics Department {M. I.. B.), Roswell Park Memorial Institute, Buffalo. New York, the Pathology Department, Children's Hospital. Buffalo, New York Ill. 1.1 and The Cancer Center, Southwest Biomedical Research Institute. Scottsdale. Arizona {A. A. S.). Address reprint requests to: AveW A. Sandberg, M.D., The C'ancer Center, Southwest Biomedical Research Institute. 6401 E. Thomas Road, Scottsdale, AZ 85251. Received December 1. 1988; accepted January 27. 1989.
125 ~ 1989 Elsevier Science Publishing Co., Inc. 655 Aw~nueof the Americas. New York, NY 10010
Cancer Genet Cytogenet 39:125-131 (1989) 0165-4608,'89.'$03.50
126
c. Sreekantaiah et al. pressure was obtained from the mother. Examination at 2 weeks of age by the pediatrician was described to be within normal limits. Family history, birth history, and pregnancy were unremarkable. Cranial ultrasound revealed an enlarged lateral and third ventricle suggesting communicating hydrocephalus. Preoperative evaluation v¢ith c-omputerized tomography (CT) scan and magnetic: resonance imaging (MRI) revealed a soft tissue mass arising in the area of the pineal gland. The baby was initially treated with serial ventric:ular laps to relieve the hydroc:ephalus, This was complic:ated by ventriculitis with c:oagulase negative staphylococcus, which was treated with antibiotics. Cerebral spinal fluid remained free of turnor cells. The baby u n d e r w e n t surgery for operative diagnosis, during which most of the tumor mass was removed and the hydrocephalus relieved. Pathologic examination revealed that the tumor was composed of a relatively homogeneous population of small and middle-sized polygonal cells with dense and uniform c:hromatin and occasional mitoses. A number of vascular structures were seen in the background, with the tumor cells forming a palisade around them in a "rosetting" fashion. A diagnosis of immature round cell tumor consistent with pineoblastoma was made IFigs. 1 and 2). Subsequent MRI, however, showed that the tumor mass continued to impinge on a third ventricle. The baby had plac:ement of a VP shunt with subsequent revision secondary to shunt obstruction, tie also had placement of a Broviac catheter. Following recovery from surgery, the patient was placed on a multiagent chromotherapy protocol that included high-dose c y c l o p h o s p h a m i d e , vincristine, cis-plati-
F i g u r e 1 Small cells with pyknotic nuclei and without well-defined cytoplasm forming no definite pattern. A mitotic figure is in the c:enter [H&E ×500).
Deletion 11 q in Pineoblastoma
12 7
t
Figure 2
Tumor cells forming a rosette in the center (H&E × 500].
num, and VP-16. This was in accordance with Pediatric Oncology Group protocol 8633-4. This protocol was designed for the treatment of infants under 3 years of age with malignant brain tumors in an effort to delay radiotherapy at least until the child's third birthday, as the long-term effects of high-dose radiation to an infant's brain are devasting in terms of neurologic anti intellectual development. The child received one cycle of this therapy, but unfortunately developed progressive disease by CT scan evaluation. He then received two cycles of (;HIP, a platinum analogue undergoing phase II study, but his disease continued to progress. Most recently, he has received a 3-week course of ,~-interferon without apparent effects. The child at this time is alive with progressive disease.
MATERIALS AND METHODS The tumor tissue, obtained as small pieces, was minced finely in a petri dish with scissors, transferred into culture flasks, and grown at 37°C with 5% CO2 in RPMI1640 growth m e d i u m and 17% fetal calf serum. The time of harvest of the cultures was i n d i v i d u a l i z e d for each flask. Depending on the mitotic: activity, the flasks were harvested for cytogenetic analysis at intervals of 4, 8, and 11 days in culture by the methotrexate synchronization technique [14]. The cells were exposed to a hypotonic solution for 30 minutes and fixed in 3:1 m e t h a n o l : a c e t i c acid fixative. Air-dried slides were G b a n d e d using Wright stain [14]. The karyotypes were expressed according to the standard nomenclature [15]. Chromosome analyses of phytohemagglutinin (PHA) stimulated peripheral blood cultures were also done to determine the i:nnstitutional karyotype.
128
c. Sreekantaiah et al.
RESULTS
Twenty-six G-banded metaphases were analyzed karyotypically. Twenty-five cells revealed the following karyotype: 46,XY,del(11)(q13.1q13.53. One cell showed a del(1)(p31p36) in addition to the 1 1 q - . The interstitial deletion of chromosome 11q is illustrated in Figures 3a and b. Analysis of PHA-stilnulated peripheral blood lymphocytes showed a normal male karyotype, 46,XY. DISCUSSION
Karyotypic analyses of various human malignancies have demonstrated correlations between specific chromosome rearrangements and types of neoplasia [16, 171. Evidence is also available that the sites of consistent rearrangements contain genes of critical importance in malignant transformation [18]. In tumors of the nervous system, n o n r a n d o m chromosome changes have been reported in meningiomas 14-7[, gliomas [8, 91, medulloblastomas [10[, and neuroblastomas [11,121. Mole(:ular studies have shown amplification of the NMYC oncogene in human neuroblastomas [19] and overexpression of the SIS oncogene [20] and amplification of the ERB oncogene in gliomas [211. We report a case of pineoblastoma, a rare brain tulnor (tumors of the Figure 3 a. Schematic presentation of the deletion 1lq in the patient. "l'hc arrows enclose the sc~gment lost in the deletion, t3. Partial karyotypes showing the del(1 l)(q13.1q13.51.
4P
11
a
"
11 der (11) b
Deletion 11q in Pineoblastoma
129
pineal region represent 0.4-4.2% of all brain tumors I22]) with a consistent deleticm of band 11q13. Aberrations of c h r o m o s o m e 11 have been associated with a significant number of neoplasms and genetic diseases. Four regions on chromosome 11 are frequently involved in cancer-related breakpoints, p15, p13, q13, and q23 [23]. Involvement of band 11q13 in our case is significant for a number of reasons. Except for one cell with an additional interstitial deletion of l p , deletion of 11q13 was the only detectable change in all other cells. This may thus represent the primary change capable of initiating or playing a role in the malignant transformation [24]. Abnormalities of c h r o m o s o m e 1 have been implicated in providing tumor cell populations with growth advantage [25]: the one cell with l p - in our case might represent the appeara n t e of a second clcme of cells with a sec:ondary chromosome c:hange, influencing progression of the malignancy. Band 11q13 is a fragile site [26], and fragile sites have been associated with breakpoints of n o n r a n d o m structural chromosome aberrations in specific neoplasms as well as oncogene locations [27]. They have also been postulated to facilitate c:hromosome rearrangements [28]. The presence of the fragile site at this band may have thus predisposed to the rearrangement. The oncogenes, abnormal expression of which are presumed to be responsible for the neoplastic phenotype, localized to this region include BCL-1 [29] and INT-2 [30]. BCL-1 has been implicated in the malignant transformation of B-cell malignanc:ies [31] and INT-2 is associated with the development of murine m a m m a r y tumors [32]. The potential significance of this association between the oncogene location and the deletion is not clear. Molecular analysis would help to determine whether there is any causal associaticm. Reports on the cytogenetic analyses of pineoblastomas are few. The two cases reported 113] formed a part of a larger series of 21 pediatric brain tumors analyzed anct could not be assessed completely because of poor chromosome quality. Both pineoblastomas occurred following hereditary retinoblastoma and were analyzed after 2 days in culture. One patient reportedly had abnormalities of chromosome 1, del(1)(p13p21) and der[1)t(1;?)(p36;?) and the other a lq ~- and a Dq ~ chromosome. It would have been interesting if abnormalities of chromosome 11 had been detected in the above two cases. Among other neurogenic neoplasms, band 11q13 has been reported to be involved in a neuroblastoma [101 and in a supratentorial epenctymoma [331. Thus, although more subtle methods of gene analysis would aid in the elucidation of the molecular genesis of the neoplasm, conventional G banding is essential for initial cytogenetic characterization of chromosomal abnormalities and the establishment of specific: chromosome changes. Analysis of more such cases will help determine the etiologic importance and role of chromosome 11 abnormalities in brain neoplasms, particularly in the pineal region. The authors thank Joyce Romano for technical assistance and Diane Blake Smith for clerical assistance. This work was funded by a grant from the Association for the Research of Childhooct Cancer {AROCC) and the Mae Stone Goode Foundation. Buffalo, New York. REFERENCES
1. Cancer Facts and Figures (1981): American Cancer Society, New York. 2. DeVita VT, Hellman S, Rosenberg SA, eds. (1982): Cancer: Principles and Practice of Ontology. Philadelphia: J. B. Lippincott Co. 3. Sano K (1983): Tumors in the pineal region (with special reference to pinealoma). In: Brain Tumors in the Young, Anador LV, ed. Charles C. Thomas, Springfield, pp. 634-654.
130
c. S r e e k a n t a i a h et al.
4. Mark J (1977): Chromosomal abnormalities and their specificity in human neoplasia: An assessment of recent observations by banding techniques. Adv Cancer Res 24:165-222. 5. Zankl H, Zang KD (1980): Correlations between clinical and cytogenetical data in 180 meningiomas. Cancer Genet Cytogenet 1:351-356. 6. AI Saadi A, l.atimer F, Madercic M, Robbins T (1987): Cytogenetic studies of human brain tumors and their clinical significance. I1. Meningioma. Cancer Genet Cytogenet 26:127-141. 7. Maltby EL, Ironside JW, Battersby RDE (1988): Cytogenetic studies on 50 meningiolnas. Cancer Genet Cytogenet 31 : 199- 210. 8. Bigner SH (1987):Chromosomal studies in malignant gliomas. In: Brain On(:ology, Biology, Diagnosis and Therapy, Chatel M. Darcel t:, Pecker J, eds. Martinus Nijhoff, I)ordrecht, pp. 21-23. 9. Rey JA. Bell() MJ, de Campos JM, Kusak ME, Moreno S (1987): Chromosomal composition of a series of 22 human low-grade gliomas. Cancer Genet Cytogenet 29:223-2:37. 10. Bigner SH, Mark J, Friedman HS. Biegel JA, Bigner DI) (1988): Structural chromosomal abnormalities in human medulloblastoma. Cancer Genet Cytogenet 30:91-101. 11. Brodeur GM, Green AA, Hayes FA, Williams KJ, Williams DL. Tsiatis AA (1981): Cytogenetic features of human neuroblastomas and cell lines. Cancer Res 41:4678-4686. 12. Gilbert F, Balaban G, Moorhead P, Bianchi I), Schlesinger M (1982): Abnormalities of chromosome l p in human neuroblastoma tumors and cell lines. Cancer Genet Cytogenet 7:33-42. 13. Griffiu CA, Hawkins AL, Packer RJ, Rorke I.B, Emmanuel BS (1988]: Chromosome abnormalities in pediatric brain tumors. Cancer Res 48:175-180. 14. Yunis JJ (1981): New chromosome techniques in the stud.,,' of human neoplasia. Hum Pathol 12:540-549. 15. ISCN (1985): An International System for Human Cytogenetic Nomenclature, Harnden DG, Klinger HP (eds.); published in collaboration with Cytogenet Cell Genet (Karger, Basel, 1985): also in Birth Defects: Original Article Series, Vol. 21, No. 1 (March of Dimes Birth Defects Foundation, New York, 1985). 16. Sandberg AA {1985}: Application of cytogenetics in neoplastic diseases. CRC Critical Reviews in Clinical Laboratory Sciences 22:219-274. 17. Sandberg AA, Turc-Carel C (1987}: The cytogenetics of solid tumors: Relation to diagnosis, classification and pathology. Cancer 59:387-395. 18. Yunis JJ (1986}: Chromosomal rearrangements, genes and fragile sites in cancer: Clinical and biologic implications. In: Important Advances in Oncology-1986, DeVita V, Hellman S, Rosenberg S, eds. JP Lippincott, Philadelphia. pp. 93-128. 19. Schwab M (1987): Amplification of N-myc in human neuroblastomas. In: Oncogenes and Growth l:actors, Branshow R, Prentis S, eds. New York, Elsevier, pp. 50-58. 20. Shapiro JR (19861: Biology of glimnas: Heterogeneity, oncogenes, growth factors. Semin Oncol 13:4-15. 21. Libermann TA, Nusbaum HR, Razor N, Kris R, Lax I, Soreg H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J (1985): Amplification, enhanced expression and possible rearrangements of the EGF receptor gene in primary human brain tumors of glial origin. Nature 313:143-147. 22. Cohen ME, Duffner PK (1984): Brain Tumors in Children. Principles of Diagnosis and Treatment. New York, Raven Press, pp. 232-244. 23. Shows TB, Davis LM, Qin S, Nowak NJ (1986}: The chromosome 11 gene map: Genes for growth and development, Wilms' tumor deletions, and cancer chromosome breakpoints, Cold Spring Harbor Symposia on Quantitative Biology, Vol LI, Cold Spring Harbor Laboratory. pp. 867-877. 24. Mitelman F, Levan G (1981}: Clustering of aberrations to specific chromosomes in h u m a n neoplasms. IV. A survey of 1,871 cases, Hereditas 95:79-139. 25. Douglass EC, Green AA, Hayes FA, Etcubanas E, Horowitz M, Wilimas JA (1985}: Chromosome 1 abnormalities: A common feature of pediatric solid tumors. J Natl Cancer Inst 75:51-54. 26. Berger R, Bloomfield CD, Sutherland GR (1985): Report of the committee on chromosome rearrangements in neoplasia and on fragile sites. Eighth International Workshop on Human Gene Mapping. Cytogenet Cell Genet 40:490-535.
Deletion
1 lq
131
in Pineoblastoma
27. De Braekeleer cancer. Hum 28. Yunis
M, Smith B, Lin CC (1985): Genet 69:112-116.
JJ, Soreng
AL (1984):
Constitutive
Fragile
fragile
sites and
structural
sites and cancer.
Science
rearrangements
in
226:1199-1204.
29. Tsujimoto Y, Yunis J, Onorato-Showe L, Erikson J, Nowell PC, Croce CM (1984): Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11:14) chromosomal translocation. Science 224:1403-1406. 30. Casey G, Smith R, McGillivrary D, Peters D, Dickson mosome assignment of the human homolog of int-2, Biol 6:502-510. 31. Tsujimoto Y, Jaffe E, Cossman J, Gerhan breakpoints on chromosome 11 in human translocation. Nature 315:340-345. 32. Dickson C, Smith R, Brookes S, Peters virus: Proviral activation of a cellular 37:529-536.
C (1986): Characterization a potential proto-oncogene.
and chroMol Cell
J, Nowell PC, Croce CM (1985): Clustering of B-cell neoplasms with the t(11;14) chromosome
G (1984):Tumorigenesis gene in the common
33. Dal Cin P, Sandberg AA (1988): Cytogenetic Cancer Genet Cytogenet 30:289-293.
findings
by mouse mammary tumor integration region int-2. Cell
in a supratentorial
ependymoma.
ABSTRACT: A case of pineohlastama with an interesting c.vtogenetic abnormality is reported. ('hromosomal analysis rff cultured cells from the tumor of a lO-week-ald white mah: revealed an interstitial deletion of the long arm of chromosome 11, del(ll)lq13.1q13.51. Tumors o.f the pineal region are relatively rare, and this is the .first report of a pineoblastama with del(1 lqJ.
INTRODUCTION Primary tumors of the central nervous system (CNS) comprise 2 - 5 % of all neoplasms and account for approximately 2% of all cancer deaths [1]. In children, brain tumors are second only to leukemia and comprise the most c o m m o n group of solid tumors of the young constituting 20% of all pediatric neoplasms [2]. The pediatric brain tumors are known to differ significantly in histology and clinical behavior from those of adults [2]. Pineal tumors consist of a variety of tumors unified by their c o m m o n location and not by any histologic similarities. The pineoblastomas considered to be primitive neuroectodermal tumors are poorly differentiated, small-cell tumors derived from pineal glandular cells. Their occurrence is extremely rare. and they show a marked male p r e d o m i n a n c e [3]. A number of specific c h r o m o s o m e abnormalities have been described in CNS tumors and other neurogenic tumors, notably meningiomas [4-7], gliomas [8, 9], medulloblastomas [10], and neuroblastomas [11, 12]. Reports on the cytogenetics of pineoblastomas are scarce; only two cases having been reported [13]. We describe a 10-week-old male baby with pineoblastoma and deletion of 11q.
CASE REPORT The patient was presented to his pediatrician at 6 weeks of age for routine examination and was noted to have a large head with bulging fontanelle. A history of downward gaze for approximately 3 weeks and lack of other signs of increased intracranial
From tile Cytogenetics Laboratory {C. S.) anti Pediatrics Department {M. I.. B.), Roswell Park Memorial Institute, Buffalo. New York, the Pathology Department, Children's Hospital. Buffalo, New York Ill. 1.1 and The Cancer Center, Southwest Biomedical Research Institute. Scottsdale. Arizona {A. A. S.). Address reprint requests to: AveW A. Sandberg, M.D., The C'ancer Center, Southwest Biomedical Research Institute. 6401 E. Thomas Road, Scottsdale, AZ 85251. Received December 1. 1988; accepted January 27. 1989.
125 ~ 1989 Elsevier Science Publishing Co., Inc. 655 Aw~nueof the Americas. New York, NY 10010
Cancer Genet Cytogenet 39:125-131 (1989) 0165-4608,'89.'$03.50
126
c. Sreekantaiah et al. pressure was obtained from the mother. Examination at 2 weeks of age by the pediatrician was described to be within normal limits. Family history, birth history, and pregnancy were unremarkable. Cranial ultrasound revealed an enlarged lateral and third ventricle suggesting communicating hydrocephalus. Preoperative evaluation v¢ith c-omputerized tomography (CT) scan and magnetic: resonance imaging (MRI) revealed a soft tissue mass arising in the area of the pineal gland. The baby was initially treated with serial ventric:ular laps to relieve the hydroc:ephalus, This was complic:ated by ventriculitis with c:oagulase negative staphylococcus, which was treated with antibiotics. Cerebral spinal fluid remained free of turnor cells. The baby u n d e r w e n t surgery for operative diagnosis, during which most of the tumor mass was removed and the hydrocephalus relieved. Pathologic examination revealed that the tumor was composed of a relatively homogeneous population of small and middle-sized polygonal cells with dense and uniform c:hromatin and occasional mitoses. A number of vascular structures were seen in the background, with the tumor cells forming a palisade around them in a "rosetting" fashion. A diagnosis of immature round cell tumor consistent with pineoblastoma was made IFigs. 1 and 2). Subsequent MRI, however, showed that the tumor mass continued to impinge on a third ventricle. The baby had plac:ement of a VP shunt with subsequent revision secondary to shunt obstruction, tie also had placement of a Broviac catheter. Following recovery from surgery, the patient was placed on a multiagent chromotherapy protocol that included high-dose c y c l o p h o s p h a m i d e , vincristine, cis-plati-
F i g u r e 1 Small cells with pyknotic nuclei and without well-defined cytoplasm forming no definite pattern. A mitotic figure is in the c:enter [H&E ×500).
Deletion 11 q in Pineoblastoma
12 7
t
Figure 2
Tumor cells forming a rosette in the center (H&E × 500].
num, and VP-16. This was in accordance with Pediatric Oncology Group protocol 8633-4. This protocol was designed for the treatment of infants under 3 years of age with malignant brain tumors in an effort to delay radiotherapy at least until the child's third birthday, as the long-term effects of high-dose radiation to an infant's brain are devasting in terms of neurologic anti intellectual development. The child received one cycle of this therapy, but unfortunately developed progressive disease by CT scan evaluation. He then received two cycles of (;HIP, a platinum analogue undergoing phase II study, but his disease continued to progress. Most recently, he has received a 3-week course of ,~-interferon without apparent effects. The child at this time is alive with progressive disease.
MATERIALS AND METHODS The tumor tissue, obtained as small pieces, was minced finely in a petri dish with scissors, transferred into culture flasks, and grown at 37°C with 5% CO2 in RPMI1640 growth m e d i u m and 17% fetal calf serum. The time of harvest of the cultures was i n d i v i d u a l i z e d for each flask. Depending on the mitotic: activity, the flasks were harvested for cytogenetic analysis at intervals of 4, 8, and 11 days in culture by the methotrexate synchronization technique [14]. The cells were exposed to a hypotonic solution for 30 minutes and fixed in 3:1 m e t h a n o l : a c e t i c acid fixative. Air-dried slides were G b a n d e d using Wright stain [14]. The karyotypes were expressed according to the standard nomenclature [15]. Chromosome analyses of phytohemagglutinin (PHA) stimulated peripheral blood cultures were also done to determine the i:nnstitutional karyotype.
128
c. Sreekantaiah et al.
RESULTS
Twenty-six G-banded metaphases were analyzed karyotypically. Twenty-five cells revealed the following karyotype: 46,XY,del(11)(q13.1q13.53. One cell showed a del(1)(p31p36) in addition to the 1 1 q - . The interstitial deletion of chromosome 11q is illustrated in Figures 3a and b. Analysis of PHA-stilnulated peripheral blood lymphocytes showed a normal male karyotype, 46,XY. DISCUSSION
Karyotypic analyses of various human malignancies have demonstrated correlations between specific chromosome rearrangements and types of neoplasia [16, 171. Evidence is also available that the sites of consistent rearrangements contain genes of critical importance in malignant transformation [18]. In tumors of the nervous system, n o n r a n d o m chromosome changes have been reported in meningiomas 14-7[, gliomas [8, 91, medulloblastomas [10[, and neuroblastomas [11,121. Mole(:ular studies have shown amplification of the NMYC oncogene in human neuroblastomas [19] and overexpression of the SIS oncogene [20] and amplification of the ERB oncogene in gliomas [211. We report a case of pineoblastoma, a rare brain tulnor (tumors of the Figure 3 a. Schematic presentation of the deletion 1lq in the patient. "l'hc arrows enclose the sc~gment lost in the deletion, t3. Partial karyotypes showing the del(1 l)(q13.1q13.51.
4P
11
a
"
11 der (11) b
Deletion 11q in Pineoblastoma
129
pineal region represent 0.4-4.2% of all brain tumors I22]) with a consistent deleticm of band 11q13. Aberrations of c h r o m o s o m e 11 have been associated with a significant number of neoplasms and genetic diseases. Four regions on chromosome 11 are frequently involved in cancer-related breakpoints, p15, p13, q13, and q23 [23]. Involvement of band 11q13 in our case is significant for a number of reasons. Except for one cell with an additional interstitial deletion of l p , deletion of 11q13 was the only detectable change in all other cells. This may thus represent the primary change capable of initiating or playing a role in the malignant transformation [24]. Abnormalities of c h r o m o s o m e 1 have been implicated in providing tumor cell populations with growth advantage [25]: the one cell with l p - in our case might represent the appeara n t e of a second clcme of cells with a sec:ondary chromosome c:hange, influencing progression of the malignancy. Band 11q13 is a fragile site [26], and fragile sites have been associated with breakpoints of n o n r a n d o m structural chromosome aberrations in specific neoplasms as well as oncogene locations [27]. They have also been postulated to facilitate c:hromosome rearrangements [28]. The presence of the fragile site at this band may have thus predisposed to the rearrangement. The oncogenes, abnormal expression of which are presumed to be responsible for the neoplastic phenotype, localized to this region include BCL-1 [29] and INT-2 [30]. BCL-1 has been implicated in the malignant transformation of B-cell malignanc:ies [31] and INT-2 is associated with the development of murine m a m m a r y tumors [32]. The potential significance of this association between the oncogene location and the deletion is not clear. Molecular analysis would help to determine whether there is any causal associaticm. Reports on the cytogenetic analyses of pineoblastomas are few. The two cases reported 113] formed a part of a larger series of 21 pediatric brain tumors analyzed anct could not be assessed completely because of poor chromosome quality. Both pineoblastomas occurred following hereditary retinoblastoma and were analyzed after 2 days in culture. One patient reportedly had abnormalities of chromosome 1, del(1)(p13p21) and der[1)t(1;?)(p36;?) and the other a lq ~- and a Dq ~ chromosome. It would have been interesting if abnormalities of chromosome 11 had been detected in the above two cases. Among other neurogenic neoplasms, band 11q13 has been reported to be involved in a neuroblastoma [101 and in a supratentorial epenctymoma [331. Thus, although more subtle methods of gene analysis would aid in the elucidation of the molecular genesis of the neoplasm, conventional G banding is essential for initial cytogenetic characterization of chromosomal abnormalities and the establishment of specific: chromosome changes. Analysis of more such cases will help determine the etiologic importance and role of chromosome 11 abnormalities in brain neoplasms, particularly in the pineal region. The authors thank Joyce Romano for technical assistance and Diane Blake Smith for clerical assistance. This work was funded by a grant from the Association for the Research of Childhooct Cancer {AROCC) and the Mae Stone Goode Foundation. Buffalo, New York. REFERENCES
1. Cancer Facts and Figures (1981): American Cancer Society, New York. 2. DeVita VT, Hellman S, Rosenberg SA, eds. (1982): Cancer: Principles and Practice of Ontology. Philadelphia: J. B. Lippincott Co. 3. Sano K (1983): Tumors in the pineal region (with special reference to pinealoma). In: Brain Tumors in the Young, Anador LV, ed. Charles C. Thomas, Springfield, pp. 634-654.
130
c. S r e e k a n t a i a h et al.
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in a supratentorial
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