Novel truncating germline variant reinforces as a susceptibility gene for familial non-medullary thyroid cancer.

Background: It has long been observed that there are families in which non-medullary thyroid cancer (NMTC) occurs, but few syndromes and genes have been described to date. Proteins in the shelterin complex have been implied in cancer. Here, we have studied shelterin genes in families affected by NMTC (FNMTC).

Methods: We performed whole-exome sequencing (WES) in 10 affected individuals from four families with at least three affected members. Polymerase chain reaction (PCR) and Sanger sequencing were performed to search for variants in the gene in 40 FNMTC families. TINF2 transcripts and loss of heterozygosity (LOH) were studied in several affected patients of one family.

Results: We found the c.507G>T variant in heterozygosis in the gene in one family, co-segregating in all five affected members. This variant affects the normal splicing. LOH was not observed.

Conclusions: Our results reinforce the gene as a susceptibility cause of FNMTC suggesting the importance of location of frameshift variants in . According to our data and previous literature, pathogenic variants appear to be a significant risk factor for the development of NMTC and/or melanoma.