Age-related sperm mutations associated with testicular tumors
Nature Genetics
October 26, 2009
A rare type of benign testicular tumor is associated with genetic mutations arising from paternal age-effect mutations, which are inherited from fathers that are older than the population mean. As discussed in the study published online this week in Nature Genetics, this type of cancer is caused by the same paternal age-effect mutation that leads to the lethal neonatal disorder Thanatophoric dysplasia (TD).
Since paternal age-effect mutations are thought to confer a growth advantage to mutant sperm, Andrew Wilkie and colleagues hypothesized that these mutant sperm might also progress to testicular tumors. The authors analyzed 30 samples of spermatocytic seminomas, a rare type of benign testicular tumor with a mean age of onset of about 54 years. The same mutation in the gene FGFR3 that leads to TD was found in two cases of spermatocytic seminoma.
Sequencing of sperm DNA from healthy men of different ages shows that this mutation increases with paternal age. The scientists found that the same cellular event ― a mutation in FGFR3 in sperm ― can lead to genetic disorders in an individual's offspring, as well as increase risk of testicular tumors in that individual.
doi: 10.1038/ng.470
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