HABP2 G534E Mutation in Familial Nonmedullary Thyroid Cancer

Papillary thyroid cancer (PTC) is a common endocrine malignancy, accounting for nearly 90% of all thyroid cancers. About 5% of PTC is hereditary familial nonmedullary thyroid cancer (FNMTC). No general susceptibility gene is known for FNMTC. An oncogenic HABP2 G534E mutation has been recently reported in one FNMTC kindred, suggesting that HABP2 is a susceptibility gene for FNMTC. Because of the limited kindred studied, how commonly this gene is responsible-and hence how important clinically it is-for FNMTC remains to be answered. By investigating a large number of FNMTC kindreds in the present study, we identified HABP2 G534E in several independent kindreds of FNMTC. The overall prevalence of HABP2 G534E was six per 43 (14.0%) PTC patients from the 29 kindreds and four per 29 (13.8%) kindreds. None of the subjects with benign thyroid neoplasm or the normal subjects from these kindreds had this mutation. These results are consistent with HABP2 G534E being a susceptibility gene in a subgroup of FNMTC, providing important diagnostic implications for this hereditary thyroid cancer.