Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer

ORIGINAL ARTICLE

Brief Report:

S.K. Gara and Others

N Engl J Med 373:448 DOI: 10.1056/NEJMoa1502449 Share: 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. Supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the patients and their family members for participating in our study, the health care providers who referred them to us for evaluation through our clinical protocol, and our colleagues Drs. Stephen J. Marx and Karel Pacak for reviewing an earlier version of the manuscript and providing helpful suggestions. SOURCE INFORMATION From the Endocrine Oncology Branch (S.K.G., L.Z., D.P., E.K.), Bioinformatics Core (L.J.) and Laboratory of Pathology (M.J.M.), Center for Cancer Research, and the Office of Science and Technology Resources (M.C.), National Cancer Institute, and the Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.K.A.) — both in Bethesda, MD. Address reprint requests to Dr. Kebebew at the Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, CRC, Rm. 4W-5952, 10 Center Dr., MSC-1201, Bethesda, MD 20892-1201, or atkebebewe@mail.nih.gov.