HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer

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

    Research output: Contribution to journalArticle

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    Abstract

    © 2016 The Author(s).
    Background: 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. 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 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. Results: 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). Conclusions: 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.
    Original languageEnglish
    Pages (from-to)1-6
    JournalBMC Medical Genetics
    Volume17
    Issue number1
    DOIs
    Publication statusPublished - 17 Aug 2016

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    Exome
    Thyroid Neoplasms
    Mutation
    Neoplasm Genes
    Tumor Suppressor Genes
    Population
    Papillary Thyroid cancer
    DNA
    Health
    Research
    Genetic Background

    Cite this

    @article{607bc05841894a239dbc09c5f971dbe1,
    title = "HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer",
    abstract = "{\circledC} 2016 The Author(s).Background: 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. 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 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. Results: 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). Conclusions: 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.",
    author = "Weeks, {Alexia L.} and Wilson, {Scott G.} and L. Ward and Jack Goldblatt and Jennie Hui and Walsh, {John P.}",
    year = "2016",
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    language = "English",
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    HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer. / Weeks, Alexia L.; Wilson, Scott G.; Ward, L.; Goldblatt, Jack; Hui, Jennie; Walsh, John P.

    In: BMC Medical Genetics, Vol. 17, No. 1, 17.08.2016, p. 1-6.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - HABP2 germline variants are uncommon in familial nonmedullary thyroid cancer

    AU - Weeks, Alexia L.

    AU - Wilson, Scott G.

    AU - Ward, L.

    AU - Goldblatt, Jack

    AU - Hui, Jennie

    AU - Walsh, John P.

    PY - 2016/8/17

    Y1 - 2016/8/17

    N2 - © 2016 The Author(s).Background: 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. 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 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. Results: 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). Conclusions: 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.

    AB - © 2016 The Author(s).Background: 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. 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 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. Results: 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). Conclusions: 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.

    U2 - 10.1186/s12881-016-0323-1

    DO - 10.1186/s12881-016-0323-1

    M3 - Article

    VL - 17

    SP - 1

    EP - 6

    JO - BMC Medical Genetics

    JF - BMC Medical Genetics

    SN - 1471-2350

    IS - 1

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