A Germline < i > CHEK2 < /i > Mutation in a Family with Papillary Thyroid Cancer.

A Germline <i>CHEK2</i> Mutation in a Family with Papillary Thyroid Cancer. Thyroid. 2020 Feb 11;: Authors: Zhao Y, Yu T, Chen L, Xie D, Wang F, Fu L, Cheng C, Li Y, Zhu X, Miao G Abstract Approximately 5% of all cases of PTC are inherited. However, the susceptibility gene(s) for nonsyndromic familial papillary thyroid carcinoma (FPTC) remain unclear. We performed whole genome sequencing (WGS) of peripheral-blood DNA samples from two affected family members with PTC. <i>CHEK2</i> transcript expression and the protein levels of CHK2 and p53 were evaluated in the thyroid tissues from two affected members of the kindred and sporadic PTC cases. The entire <i>CHEK2</i> coding sequence was examined by Sanger sequencing in blood DNA samples from 242 sporadic PTC patients. We identified a novel heterozygous germline mutation in <i>CHEK2</i> (c.417C→A) that was detected in all available affected members of a kindred with FPTC. This variant was found in only one out of 264,200 persons in the Genome Aggregation Database and the NHLBI Trans-Omics for Precision Medicine program. The <i>CHEK2</i> c.417C→A variant introduces a premature termination codon (Y139X). We found reduced CHK2 protein expression in tumor samples from the two patients who carried the variant as compared to sporadic cases without the variant. The Y139X loss-of-function variant led to reduced p53 phosphorylation a...
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research