HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer.

Alexia L Weeks,Lynley Ward,John P Walsh,Jack Goldblatt,Scott G Wilson,Jennie Hui

doi:10.1186/s12881-016-0323-1

Abstract

BackgroundThe genetic basis of nonsyndromic familial nonmedullary thyroid cancer (FNMTC) is poorly understood. A recent study identified HABP2 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.MethodsSanger 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 in HABP2 and the thyroid cancer susceptibility genes SRGAP1, NKX2-1, SRRM2 and FOXE1. The population prevalence of the G534E variant in HABP2 was examined in two independent cohorts.ResultsHeterozygosity for the G534E variant in HABP2 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 in HABP2, SRGAP1, NKX2-1, SRRM2 or FOXE1. Heterozygosity for the G534E variant in HABP2 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).ConclusionsThe G534E variant in HABP2 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.

Highlights

The genetic basis of nonsyndromic familial nonmedullary thyroid cancer (FNMTC) is poorly understood
We investigated a collection of 37 FNMTC kindreds for the presence of this variant using Sanger sequencing
Sanger sequencing was performed on peripheral blood DNA from probands from each kindred in order to detect the G534E variant in hyaluronan binding protein 2 (HABP2)

Summary

Introduction

The genetic basis of nonsyndromic familial nonmedullary thyroid cancer (FNMTC) is poorly understood. Nonsyndromic familial nonmedullary thyroid cancer (FNMTC) is thought to account for approximately 3.5–10 % of all NMTC [6]. It is defined by the presence of thyroid cancer of follicular cell origin in 2 or more first-degree relatives, in the absence of a recognized familial cancer syndrome (such as Cowden syndrome or familial adenomatous polyposis) [7]. Both familial and sporadic NMTC are more common in women than men [8]

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Conclusion