Does a common genetic event exist for familial thyroid cancer? Results from a large family with FNMTC

Abstract

Abstract Background Despite several efforts, the genetic susceptibility of familial non medullary thyroid cancer (FNMTC), has remained still elusive. Methods We performed Whole Exome Sequencing (WES) in a large family with 9 available members, 6/9 (67%) affected by FNMTC. Results We found two missense variants, with CADD score > 20: the c.C1519A (p.Pro507Thr, rs773271544) in PRKCɛ gene and the c.G1019A (p.R340Q) in CCZ1B gene. These alterations were absent in healthy subjects (n = 40) and in 30 sporadic thyroid cancer patients. The p.P507T was possibly pathogenetic by SIFT and PRKCɛ is implicated with MAPK activation by STRING. When we searched for this mutation in other families, we failed to confirm this genetic event as causative of cancer in other 20 FNMTC patients belonging to 8 kindred. Conclusions We concluded that the PRKCɛ p.Pro507Thr possibly represents a private mutation even if other studies including large FNMTC family are needed to define the percentage of familial thyroid cancer cases due this alteration.