HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Weeks, Alexia; Wilson, Scott; Ward, Lynley; Goldblatt, Jack; Hui, Jennie; Walsh, John
• Is Part Of: BMC medical genetics. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 6
• Publication Date: 2016-12
• Subjects: Papillary thyroid cancer -- Thyroid carcinoma -- Oncogenes -- HABP2; Medical genetics -- Periodicals; 616.04205
• DOI: 10.1186/s12881-016-0323-1
• Languages: English
• ISSNs: 1471-2350

Abstract

Abstract Background The genetic basis of nonsyndromic familial nonmedullary thyroid cancer (FNMTC) is poorly understood. A recent study identifiedHABP2 as a tumor suppressor gene and identified a germline variant (G534E) in an extended FNMTC kindred. The relevance of this to other FNMTC kindreds is uncertain. Methods Sanger sequencing was performed on peripheral blood DNA from probands from 37 Australian FNMTC kindreds to detect the G534E variant. Whole exome data from 59 participants from 20 kindreds were examined for mutations inHABP2 and the thyroid cancer susceptibility genesSRGAP1, NKX2-1, SRRM2 andFOXE1. The population prevalence of the G534E variant inHABP2 was examined in two independent cohorts. Results Heterozygosity for the G534E variant inHABP2 was found in 1 of 37 probands (2.7 %), but did not cosegregate with disease in this kindred, being absent in the proband's affected sister. From whole exome data, pathogenic mutations were not identified inHABP2, SRGAP1, NKX2-1, SRRM2 orFOXE1. Heterozygosity for the G534E variant inHABP2 was present in 7.6 % of Busselton Health Study participants (N = 4634, unknown disease status) and 9.3 % of TwinsUK participants (N = 1195, no history of thyroid cancer). Conclusions The G534E variant inHABP2 does not account for the familial nature of NMTC in Australian kindreds, and is common in the general population. Further research is required to elucidate the genetic basis of nonsyndromic FNMTC.