Molecular characterization of a recurring complex chromosomal translocation in two human extragonadal germ cell tumors (original) (raw)
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Cancer Genetics and Cytogenetics, 2001
Chromosome studies of pediatric germ cell tumors (GCTs) show differences in abnormalities dependent on age, sex, tumor location, and histology. Previous studies suggest that loss of 1p is associated with a malignant phenotype, while amplification of 12p, a common finding in adult testicular GCTs, is uncommon in pediatric GCTs. Fifty-three pediatric GCTs were analyzed for 1p36 loss and 12p amplification by G-banding and dual-color interphase FISH with probes for the centromere and short arm of chromosomes 1 or 12. Twelve tumors with loss of 1p36 were identified. No deletion was detected in tumors with nonmalignant histology, such that there was a significant association of 1p loss with malignancy in these tumors ( P ϭ 0.00115). Five of 18 tumors from male patients had amplification of 12p, consistent with G-band results. Combined analysis of our data with those in the literature revealed a significant correlation of 12p amplification with patient age ( P ϭ 0.000196). Amplification of 12p was only seen in one of 35 tumors from female patients. Five female GCTs had numerical abnormalities of chromosome 12, and two tumors showed complete lack of 12p. This spectrum of abnormalities differs from what is seen in the male tumors, providing further evidence for different etiologies of GCTs between the sexes.
Proceedings of the National Academy of Sciences of the United States of America, 1986
Recurring, site-specific chromosomal rearrangements are associated with several human syndromes and malignant disorders. Such nonrandom translocations involving chromosome 22 in band q11 are numerous and found to be associated with a diversity of neoplasms as well as constitutional disorders. Chromosome 11 in bands q23-q24 is similarly involved in several types of tumors as well as in a recurring constitutional reciprocal translocation with chromosome 22. Here we report the use of chromosomal in situ hybridization to compare the translocation breakpoints in the cytologically indistinguishable constitutional t(11;22) and the tumor-related t(11;22) associated with Ewing sarcoma and peripheral neuroepithelioma. We have shown that the breakpoints can be distinguished from each other with respect to the locus encoding the constant region of the Ig lambda light chain (C lambda) at 22q11 and the ETS1 locus at 11q23----q24; ETS1 has been called hu-ets-1 or human c-ets-1. The tumor-associate...
Nonrandom chromosome abnormalities in testicular and ovarian germ cell tumor cell lines
Cancer Genetics and Cytogenetics, 1990
We report the karyotypic analysis of seven testicular and one ovarian germ cell tumor (GCT) cell lines, a number of which have previously been partially investigated. An i[12p) was found in each of the testicular GCT cell lines, while it was absent in the ovarian GCT cell line. Thus, our study extends to cell lines the observation from fresh tumor tissues that i(12p) is a highly nonrandom chromosomal abnormality of testicular GCT. Additional consistent nonmndom abnormalities in the testicular GCT cell lines included the following: del(lJ~p22), del(lJ[q21), i(lq), del~TJ~q11.2), and del ). The del~12J[q14) abnormality was identi~ed in five of the cell lines investigated. This observation, together with previous detection of this marker chromosome in fresh tumor specimens by us and others, suggests that loss of genetic material on 12q may represent a primary change associated with malignant transformation of testicular germ cells. As reported in a previous study, a t(15;20J~pll;qll) translocatian was identiJied in the ovarian GCT cell line. Interesting/y, it also was seen in one testicular GCT cell line. In addition, a der(15)t(15;g0)~pl 1;q~ 1) marker chromosome was identiJied in two other testicular GCT cell lines. Thus, this reinvestigation of GCT cell lines has resolved the discrepancy regarding the occurrence of i(1 gp) in fresh tumors versus established cell lines and ldentlDed additional nonrandom abnormalities of potential importance to the development of GCTs.
Genomics, 1996
chromosomal arm (Mitelman, 1994) or loss of heterozy-A candidate tumor suppressor gene (TSG) site at gosity (LOH) of markers located on it have been re-12q22 characterized by a high frequency of loss of hetported in various tumor types (Fey et al., 1989; Sano erozygosity (LOH) and a homozygous deletion has preet viously been reported in human male germ cell tumors Schneider et al., 1995; Hahn et al., 1995). Male (GCTs). In a detailed deletion mapping analysis of 67 germ cell tumors (GCTs) have been shown to carry normal-tumor DNAs utilizing 20 polymorphic markers chromosomal deletions affecting 12q or monosomy of mapped to 12q22-q24, we identified the limits of the chromosome 12 Samaniego et al., minimal region of deletion at 12q22 between D12S377 1990; Rodriguez et al., 1992). Restriction fragment (proximal) and D12S296 (distal). We have constructed length polymorphism (RFLP) studies of male GCTs a YAC contig map of a 3-cM region of this band between have identified LOH at two sites, 12q13 and 12q22, the proximal marker D12S101 and the distal marker suggesting the presence of at least two candidate TSGs D12S346, which contained the minimal region of deleon 12q (Murty et al., 1992). The 12q22 deletions were tion in GCTs. The map is composed of 53 overlapping characterized by LOH affecting the markers D12S7 YACs and 3 cosmids onto which 25 polymorphic and and D12S12. In addition, a homozygous deletion at nonpolymorphic sequence-tagged sites (STSs) were 12q22 in one case of GCT has been identified that gave placed in a unique order. The size of the minimal refurther support to the hypothesis of a candidate TSG gion of deletion was approximately 2 Mb from overlapin this chromosomal region. As a prelude to isolating ping, nonchimeric YACs that spanned the region. We this candidate TSG, we further characterized the realso developed a radiation hybrid (RH) map of the region of deletion, constructed a physical map, and exgion between D12S101 and D12S346 containing 17 loci.
Genes, Chromosomes and Cancer, 1995
Malignant transformation may be caused by gene deregulation resulting from specific chromosomal rearrangements, by amplification, by mutations in proto-oncogenes, by loss of tumor suppressor genes, or a combination of these. We investigated the role of numerical and structural chromosomal abnormalities in I02 cytogenetically abnormal cases of primary testicular germ cell tumors of adolescents and adults (TGCT) [32 seminomas (SE) and 70 nonseminomatous germ cell tumors (NS)]. We confirmed that an isochromosome for I2p. i( I 2p), is the only consistent structural chromosomal abnormality in TGCT, present in about 70% of our cases. Both the frequency and the number of copies of i( I2p) are higher in NS than in SE. This may suggest that i( I2p) is involved in tumor progression. Besides i( I2p), several clonal structural chromosomal abnormalities were found, but none appeared t o be specific. SE and NS had chromosome numbers in the triploid range, with significantly higher numbers in SE than in NS (average modal chromosome number of 73.4 in SE and 65.0 in NS). Both in SE and NS, some chromosomes were significantly underrepresented (e.g., I I, 13, 18, and Y) and others overrepresented (e.g., 7, 8, 12, 2 I, and X). In SE, a significantly higher copy number of chromosomes 7, 15, 19, and 22 was found and a significantly lower number of chromosome 17, compared with NS. These chromosomes may play an important role in the differentiation of TGCT. Genes Chromosom Cancer /4:/33-/44 (1995). 0 1995 Wiley-Liss, Inc.
2005
Human germ cell tumors (GCTs) of neonates and infants comprise a heterogeneous group of neoplasms, including teratomas and yolk sac tumors with distinct clinical and epidemiologic features. As yet, little is known about the cytogenetic constitution of these tumors. We applied the recently developed genomewide array-based comparative genomic hybridization (array CGH) technology to 24 GCTs derived from patients under the age of 5 years. In addition, we included seven tumors derived from children and adolescents older than 5 years. In the series from those under the age of 5 years, most teratomas displayed normal profiles, except for some minor recurrent aberrations. In contrast, the yolk sac tumors displayed recurrent losses of 1p35-pter and gains of 3p21-pter and of 20q13. In the GCTs of patients older than 5 years, the main recurrent anomalies included gains of 12p and of whole chromosomes 7 and 8. In addition, gains of the 1q32-qter region and losses of the 6q24qter and 18q21-qter regions were frequent in GCTs of varied histology, independent of age. We concluded that array CGH is a highly suitable method for identifying recurrent chromosomal anomalies in GCTs of neonates and infants. The recurrent anomalies observed point to chromosomal regions that may harbor novel diagnostic/prognostic identifiers and genes relevant to the development of these neoplasms. V
Cancer Genetics and Cytogenetics, 1996
Comparative genomic hybridization (CGH) was carried out on 15 primary testicular germ cell tumors (TGCT) of adolescents and adults and two metastatic residual tumors after chemotherapeutic treatment. The results were compared with karyotypic data obtained form the same tumor specimens after direct harvesting of metaphases or short-term in vitro culture. Both techniques revealed that the most consistent abnormality in primary TGCT is gain of 12p-sequences. Although in most cases overrepresentation of the complete short arm was observed, CGH revealed a specific amplification of 121311.1-1312.1 region in two independent primary tumors. In addition, loss of (parts of) chromosome 13 (always involving q31-qter), and gain of (parts of) chromosome 7 (mostly involving ql 1), (parts of) chromosome 8, and the X chromosome were detected in more than 25% of the tumors by this latter technique. Loss of 6q15-q21 in both residual tumors analyzed may suggest a role for this anomaly in acquired resistance to chemotherapeutic treatment.