Rare De Novo Germline Copy-Number Variation in Testicular Cancer

Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
The American Journal of Human Genetics (Impact Factor: 10.93). 08/2012; 91(2):379-83. DOI: 10.1016/j.ajhg.2012.06.019
Source: PubMed


Although heritable factors are an important determinant of risk of early-onset cancer, the majority of these malignancies appear to occur sporadically without identifiable risk factors. Germline de novo copy-number variations (CNVs) have been observed in sporadic neurocognitive and cardiovascular disorders. We explored this mechanism in 382 genomes of 116 early-onset cancer case-parent trios and unaffected siblings. Unique de novo germline CNVs were not observed in 107 breast or colon cancer trios or controls but were indeed found in 7% of 43 testicular germ cell tumor trios; this percentage exceeds background CNV rates and suggests a rare de novo genetic paradigm for susceptibility to some human malignancies.

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Available from: Diane Esposito
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    • "Nevertheless, these six loci together with the “gr/gr” deletion account for less than 15% of the excess familial risk, suggesting that many more risk alleles remain unaccounted for (reviewed in [19,22]). A recent study suggested a possible role for de novo germline copy number variants (CNVs); such variants were seen in 7% of 43 TGCT trios, greater than the expected background rate of CNVs [23]. With these results in mind, whole exome/genome sequencing studies, focusing on large series of familial TGCTs is likely to be the next step in efforts to understand the genetic basis of TGCT. "
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