GermlineHABP2Mutation Causing Familial Nonmedullary Thyroid Cancer

Abstract

SUMMARY Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased HABP2 protein expression in tumor samples from affected family members, as compared with normal adjacent thyroid tissue and samples from sporadic cancers. Functional studies showed that HABP2 has a tumor-suppressive effect, whereas the G534E variant results in loss of function.

Factor VII activating protease (FSAP) regulates the expression of inflammatory genes in vascular smooth muscle and endothelial cells

“…The MI-SNP has also been associated with familial nonmedullary thyroid cancer 78 however this finding has been questioned by various researchers 79 . It was shown that MI-but not WT-FSAP overexpression increased colony formation and migration in various cell lines and vice versa when inhibiting expression of FSAP using siRNA 78 . In addition, MI-FSAP but not WT-FSAP could transform mouse fibroblasts and thereby allow anchorage independent growth in soft agar 78 .…”

ENDOCRINE TUMOURS: Advances in the molecular pathogenesis of thyroid cancer: lessons from the cancer genome

“…In addition, pedigrees displaying Mendelian-type inheritance of PTC are very rare, and large pedigrees with more than five affected individuals are exceptional. Very recently, Gara et al reported that a germline missense mutation, G534E in HABP2, was responsible for the segregation of familial non-medullary thyroid cancer in a family and occurred in 4.7% of 423 patients with thyroid carcinoma in the TCGA database (53). However, segregation of this mutation has not been seen in larger series of familial non-medullary thyroid cancer (54,55) and more evidence is needed to consistently support, or not, a role of HABP2 G534e variant in PTC.…”

Key Developments in Pediatric Endocrinology in 2015

“…Gara et al report the first genetic mutation causing nonmedullary thyroid cancer. 8 These investigators from the National Cancer Institute studied a large kindred where, over three generations, six members developed papillary thyroid cancer and one had a follicular adenoma. They identified a germline mutation in HABP2 in the affected family members.…”