HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer.
HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer.
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DOI：
10.1186/s12881-016-0323-1
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发表时间：
2016-08-17
影响因子：
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通讯作者：
Walsh JP
中科院分区：
文献类型：
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作者：
Weeks AL;Wilson SG;Ward L;Goldblatt J;Hui J;Walsh JP
非综合征型家族性非髓样甲状腺癌（FNMTC）的遗传基础知之甚少。最近的一项研究将HABP 2鉴定为肿瘤抑制基因，并在扩展的FNMTC家族中鉴定了种系变体（G534 E）。这与其他FNMTC激酶的相关性尚不确定。对来自37名澳大利亚FNMTC激酶的先证者的外周血DNA进行桑格测序，以检测G534 E变体。对来自20个基因组的59名参与者的全外显子组数据进行了HABP 2和甲状腺癌易感基因SRGAP 1、NKX 2 -1、SRRM 2和FOXE 1的突变检查。在两个独立的队列中检查HABP 2中G534 E变异的人群患病率。HABP 2基因G534 E变异的杂合性在37个先证者中发现1个（2.7%），但在这个家系中没有与疾病共分离，在先证者的患病姐妹中不存在。从全外显子组数据中，在HABP 2、SRGAP 1、NKX 2 -1、SRRM 2或FOXE 1中未鉴定出致病性突变。HABP 2中G534 E变异体的杂合性存在于7.6%的布塞尔顿健康研究参与者（N = 4634，疾病状态未知）和9.3%的TwinsUK参与者（N = 1195，无甲状腺癌病史）中。HABP 2中的G534 E变异不能解释澳大利亚Kinetics中NMTC的家族性，并且在一般人群中很常见。需要进一步的研究来阐明非综合征型FNMTC的遗传基础。
The 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. 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 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. Heterozygosity 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). The 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.