Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Am J Hum Genet. 2012 Aug 10;91(2):379-83. doi: 10.1016/j.ajhg.2012.06.019. Epub 2012 Aug 2.
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.
尽管遗传因素是早发性癌症风险的一个重要决定因素，但大多数此类恶性肿瘤似乎是无明显危险因素的散发。散发性神经认知和心血管疾病中已经观察到种系新生拷贝数变异 (CNV)。我们在 116 个早发性癌症病例-父母三体型和无病兄弟姐妹的 382 个基因组中探索了这一机制。在 107 个乳腺癌或结肠癌三体型或对照中未观察到独特的新生种系 CNV，但在 43 个睾丸生殖细胞肿瘤三体型中确实发现了 7%；这一比例超过了背景 CNV 率，表明对于某些人类恶性肿瘤，存在罕见的新生遗传易感性模式。
