Germline variants of BAP1 in the Australian population: Journal of Clinical Oncology

Research output: Contribution to journalMeeting abstract

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Germline variants of BAP1 in the Australian population : Journal of Clinical Oncology. / Walpole, Sebastian; Pritchard, Antonia; Palmer, Jane; Howlie, Madeleine; Symmons, Judith; Hamilton, Hayley; Glasson, William; Warrier, Sunil; Rolfe, Olivia; Stark, Andrew; D'Mellow, Matthew; Hayward, Nicholas.

In: Journal of Clinical Oncology, Vol. 36, No. 15 Suppl, 01.06.2018, p. e13534-e13534.

Research output: Contribution to journalMeeting abstract

Harvard

Walpole, S, Pritchard, A, Palmer, J, Howlie, M, Symmons, J, Hamilton, H, Glasson, W, Warrier, S, Rolfe, O, Stark, A, D'Mellow, M & Hayward, N 2018, 'Germline variants of BAP1 in the Australian population: Journal of Clinical Oncology' Journal of Clinical Oncology, vol 36, no. 15 Suppl, pp. e13534-e13534. DOI: 10.1200/JCO.2018.36.15_suppl.e13534

APA

Walpole, S., Pritchard, A., Palmer, J., Howlie, M., Symmons, J., Hamilton, H., ... Hayward, N. (2018). Germline variants of BAP1 in the Australian population: Journal of Clinical Oncology. Journal of Clinical Oncology, 36(15 Suppl), e13534-e13534. DOI: 10.1200/JCO.2018.36.15_suppl.e13534

Vancouver

Walpole S, Pritchard A, Palmer J, Howlie M, Symmons J, Hamilton H et al. Germline variants of BAP1 in the Australian population: Journal of Clinical Oncology. Journal of Clinical Oncology. 2018 Jun 1;36(15 Suppl):e13534-e13534. Available from, DOI: 10.1200/JCO.2018.36.15_suppl.e13534

Author

Walpole, Sebastian ; Pritchard, Antonia ; Palmer, Jane ; Howlie, Madeleine ; Symmons, Judith ; Hamilton, Hayley ; Glasson, William ; Warrier, Sunil ; Rolfe, Olivia ; Stark, Andrew ; D'Mellow, Matthew ; Hayward, Nicholas. / Germline variants of BAP1 in the Australian population : Journal of Clinical Oncology. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 15 Suppl. pp. e13534-e13534

Bibtex

@article{19e5c9b5278243949a3326a8d073f8d0,
title = "Germline variants of BAP1 in the Australian population: Journal of Clinical Oncology",
abstract = "e13534 Background: Germline mutations in the BRCA1-associated protein (BAP1) gene are linked to a large spectrum of cancers, defined as the BAP1 tumour predisposition syndrome (BAP1-TPDS). The cancers usually occurring in kindreds with BAP1-TPDS are uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, cholangiocarcinoma and meningioma. A 2017 review identified only 87 probands worldwide with germline BAP1 mutations. Methods: To better understand the frequency of BAP1-TPDS, we took a systematic BAP1 sequencing approach of a defined population. We screened Queensland uveal melanoma probands and their families for mutations in BAP1 (n = 64), identified variants from published studies from Australia and liaised with clinical genetics services Australia-wide to ascertain BAP1 germline variants. Only variants with a population frequency of <0.0005 were considered. Results: We identified 2 truncating, 1 missense, 2 synonymous, 1 intronic and 1 promoter variant in the sequencing screen (7/64). Two truncating variants were referred by the clinical genetics services and finally, 13 published variants in Australian families were identified. The 4 truncating variants occur in kindreds with classical features of BAP1-TPDS and are disease causing. Of the total 11 missense variants, only 1 occurs in a family with BAP1-TPDS phenotype, which has been previously published (p.T173C) and is predicted to impair ubiquitin hydrolase activity. In silico prediction suggests 8/9 unique missense and 1 synonymous variants either alter splicing or damage protein structure, which requires functional confirmation. The intronic variant lies 8bp into intron 13 and is of unknown consequence. Finally, the promoter variant has been reported in an Italian family with the phenotype; however, in the Australian family, incomplete family history for the proband does not allow for a full assessment. Conclusions: The detection of six definite and two likely deleterious variants in this focused assessment of BAP1 in Australia suggests mutations may be more common than indicated by literature review. This study highlights a need for a comprehensive worldwide database of germline BAP1 variants and cancers present in carriers and development of a guide to clinical testing.",
author = "Sebastian Walpole and Antonia Pritchard and Jane Palmer and Madeleine Howlie and Judith Symmons and Hayley Hamilton and William Glasson and Sunil Warrier and Olivia Rolfe and Andrew Stark and Matthew D\{textquoteleft}Mellow and Nicholas Hayward",
note = "M1 - 15_suppl",
year = "2018",
month = "6",
day = "1",
doi = "10.1200/JCO.2018.36.15_suppl.e13534",
language = "English",
volume = "36",
pages = "e13534--e13534",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "15 Suppl",

}

RIS

TY - JOUR

T1 - Germline variants of BAP1 in the Australian population

T2 - Journal of Clinical Oncology

AU - Walpole,Sebastian

AU - Pritchard,Antonia

AU - Palmer,Jane

AU - Howlie,Madeleine

AU - Symmons,Judith

AU - Hamilton,Hayley

AU - Glasson,William

AU - Warrier,Sunil

AU - Rolfe,Olivia

AU - Stark,Andrew

AU - D'Mellow,Matthew

AU - Hayward,Nicholas

N1 - M1 - 15_suppl

PY - 2018/6/1

Y1 - 2018/6/1

N2 - e13534 Background: Germline mutations in the BRCA1-associated protein (BAP1) gene are linked to a large spectrum of cancers, defined as the BAP1 tumour predisposition syndrome (BAP1-TPDS). The cancers usually occurring in kindreds with BAP1-TPDS are uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, cholangiocarcinoma and meningioma. A 2017 review identified only 87 probands worldwide with germline BAP1 mutations. Methods: To better understand the frequency of BAP1-TPDS, we took a systematic BAP1 sequencing approach of a defined population. We screened Queensland uveal melanoma probands and their families for mutations in BAP1 (n = 64), identified variants from published studies from Australia and liaised with clinical genetics services Australia-wide to ascertain BAP1 germline variants. Only variants with a population frequency of <0.0005 were considered. Results: We identified 2 truncating, 1 missense, 2 synonymous, 1 intronic and 1 promoter variant in the sequencing screen (7/64). Two truncating variants were referred by the clinical genetics services and finally, 13 published variants in Australian families were identified. The 4 truncating variants occur in kindreds with classical features of BAP1-TPDS and are disease causing. Of the total 11 missense variants, only 1 occurs in a family with BAP1-TPDS phenotype, which has been previously published (p.T173C) and is predicted to impair ubiquitin hydrolase activity. In silico prediction suggests 8/9 unique missense and 1 synonymous variants either alter splicing or damage protein structure, which requires functional confirmation. The intronic variant lies 8bp into intron 13 and is of unknown consequence. Finally, the promoter variant has been reported in an Italian family with the phenotype; however, in the Australian family, incomplete family history for the proband does not allow for a full assessment. Conclusions: The detection of six definite and two likely deleterious variants in this focused assessment of BAP1 in Australia suggests mutations may be more common than indicated by literature review. This study highlights a need for a comprehensive worldwide database of germline BAP1 variants and cancers present in carriers and development of a guide to clinical testing.

AB - e13534 Background: Germline mutations in the BRCA1-associated protein (BAP1) gene are linked to a large spectrum of cancers, defined as the BAP1 tumour predisposition syndrome (BAP1-TPDS). The cancers usually occurring in kindreds with BAP1-TPDS are uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, cholangiocarcinoma and meningioma. A 2017 review identified only 87 probands worldwide with germline BAP1 mutations. Methods: To better understand the frequency of BAP1-TPDS, we took a systematic BAP1 sequencing approach of a defined population. We screened Queensland uveal melanoma probands and their families for mutations in BAP1 (n = 64), identified variants from published studies from Australia and liaised with clinical genetics services Australia-wide to ascertain BAP1 germline variants. Only variants with a population frequency of <0.0005 were considered. Results: We identified 2 truncating, 1 missense, 2 synonymous, 1 intronic and 1 promoter variant in the sequencing screen (7/64). Two truncating variants were referred by the clinical genetics services and finally, 13 published variants in Australian families were identified. The 4 truncating variants occur in kindreds with classical features of BAP1-TPDS and are disease causing. Of the total 11 missense variants, only 1 occurs in a family with BAP1-TPDS phenotype, which has been previously published (p.T173C) and is predicted to impair ubiquitin hydrolase activity. In silico prediction suggests 8/9 unique missense and 1 synonymous variants either alter splicing or damage protein structure, which requires functional confirmation. The intronic variant lies 8bp into intron 13 and is of unknown consequence. Finally, the promoter variant has been reported in an Italian family with the phenotype; however, in the Australian family, incomplete family history for the proband does not allow for a full assessment. Conclusions: The detection of six definite and two likely deleterious variants in this focused assessment of BAP1 in Australia suggests mutations may be more common than indicated by literature review. This study highlights a need for a comprehensive worldwide database of germline BAP1 variants and cancers present in carriers and development of a guide to clinical testing.

U2 - 10.1200/JCO.2018.36.15_suppl.e13534

DO - 10.1200/JCO.2018.36.15_suppl.e13534

M3 - Meeting abstract

VL - 36

SP - e13534-e13534

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 15 Suppl

ER -

ID: 3534744