Familial/Bilateral and Sporadic Testicular Germ Cell Tumors Show Frequent Genetic Changes at Loci with Suggestive Linkage Evidence
Neoplasia, ISSN: 1476-5586, Vol: 3, Issue: 3, Page: 196-203
2001
- 28Citations
- 9Captures
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Metrics Details
- Citations28
- Citation Indexes28
- 28
- CrossRef18
- Captures9
- Readers9
Article Description
Testicular germ cell tumor (TGCT) is the most common tumor type among adolescent and young adult males. Familial clustering and bilateral disease are suggestive of a genetic predisposition among a subgroup of these patients, but susceptibility genes for testicular cancer have not yet been identified. However, suggestive linkage between disease and genetic markers has been reported at loci on chromosome arms 3q, 5q, 12q, 18q, and Xq. We have analyzed primary familial/ bilateral ( n =20) and sporadic ( n =27) TGCTs, including 28 seminomas and 19 nonseminomas, for allelic imbalance (AI) within the autosomal regions. DNA from all tumors were analyzed by fluorescent polymerase chain reaction of 22 polymorphic loci at 3q27-ter, 5q13-35.1, 12q21-ter, and 18q12-ter. All tumor genotypes were evaluated against their corresponding constitutional genotypes. The percentages of TGCTs with genetic changes at 3q, 5q, 12q, and 18q, were 79%, 36%, 53% and 43%, respectively. The frequencies at 3q and 12q in nonseminomas were significantly higher than in seminomas ( P=.003 and P =.004). In order to evaluate changes at hemizygous Xq loci, five loci were analyzed by co-amplification with an autosomal reference marker known to reveal retained heterozygosity in the tumor DNA. Gain of Xq sequences was seen in more than 50% of the tumors. The degree of amplification varied among the loci in each of five tumors, and based on these breakpoints, a common region of overlapping gains was found at X828. No significant differences were found between the frequencies of genetic changes in familial /bilateral versus sporadic tumors, an observation speaking in disfavor of the existence of a single susceptibility gene for TGCT in any of the analyzed regions. Our data suggest that gain of genetic material at distal Xq and losses at 5q and 18q contribute to establishment of seminomas, whereas imbalances at 3q as well as gain at distal part of 12q are associated with further progression into nonseminomas.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1476558601800439; http://dx.doi.org/10.1038/sj.neo.7900153; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0034891337&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/11494113; https://linkinghub.elsevier.com/retrieve/pii/S1476558601800439; https://dx.doi.org/10.1038/sj.neo.7900153
Elsevier BV
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