Centenarian Exomes as a Tool for Evaluating the Clinical Relevance of Germline Tumor Suppressor Mutations.

OBJECTIVES

The aim of the present study was to evaluate the clinical relevance of mutations in tumor suppressor genes using whole-exome sequencing data from centenarians and young healthy individuals.

METHODS

Two pools, one of centenarians and one of young individuals, were constructed and whole-exome sequencing was performed. We examined the whole-exome sequencing data of Bulgarian individuals for carriership of tumor suppressor gene variants.

RESULTS

Of all variants annotated in both pools, 5080 (0.06%) are variants in tumor suppressor genes but only 46 show significant difference in allele frequencies between the two studied groups. Four variants (0.004%) are pathogenic/risk factors according to single nucleotide polymorphism database: rs1566734 in , rs861539 in , rs203462 in , and rs486907 in .

DISCUSSION

Based on their high minor allele frequencies and presence in the centenarian group, we could reclassify them from pathogenic/risk factors to benign. Our study shows that centenarian exomes can be used for re-evaluating the clinically uncertain variants.