Homologous recombination DNA repair defects in PALB2-associated breast cancers

A Li; FC Geyer; P Blecua; JY Lee; P Selenica; DN Brown; F Pareja; SSK Lee; R Kumar; B Rivera; R Bi; S Piscuoglio; HY Wen; JR Lozada; R Gularte-Mérida; L Cavallone; M Aghmesheh; D Amor; L Andrews; Y Antill; R Balleine; J Beesley; A Blackburn; M Bogwitz; M Brown; M Burgess; J Burke; P Butow; L Caldon; I Campbell; A Christian; C Clarke; P Cohen; A Crook; J Cui; M Cummings; SJ Dawson; A De Fazio; M Delatycki; A Dobrovic; T Dudding; P Duijf; E Edkins; S Edwards; G Farshid; A Fellows; M Field; J Flanagan; P Fong; J Forbes; L Forrest; S Fox; J French; M Friedlander; DG Ortega; M Gattas; G Giles; G Gill; M Gleeson; S Greening; E Haan; M Harris; N Hayward; I Hickie; J Hopper; C Hunt; P James; M Jenkins; R Kefford; M Kentwell; J Kirk; J Kollias; S Lakhani; G Lindeman; L Lipton; L Lobb; S Lok; F Macrea; G Mann; D Marsh; SA McLachlan; B Meiser; R Milne; S Nightingale; S O’Connell; N Pachter; B Patterson; K Phillips; M Saleh; E Salisbury; C Saunders; J Saunus; C Scott; R Scott; A Sexton; A Shelling; P Simpson; A Spigelman; M Spurdle; J Stone

Journal article

Homologous recombination DNA repair defects in PALB2-associated breast cancers

A Li, FC Geyer, P Blecua, JY Lee, P Selenica, DN Brown, F Pareja, SSK Lee, R Kumar, B Rivera, R Bi, S Piscuoglio, HY Wen, JR Lozada, R Gularte-Mérida, L Cavallone, M Aghmesheh, D Amor, L Andrews, Y Antill Show all

Npj Breast Cancer | NATURE PUBLISHING GROUP | Published : 2019

DOI: 10.1038/s41523-019-0115-9

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Abstract

Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, ..

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University of Melbourne Researchers

Graham Giles Author

Geoffrey Lindeman Author

Alison Trainer Author

Ingrid Winship Author

Grants

Awarded by National Breast Cancer Foundation

Funding Acknowledgements

The authors thank the PALB2 interest group for their contributions to this study. The authors thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. Research reported in this paper was supported in part by the Breast Cancer Research Foundation and the Sarah Jenkins Fund, a Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute (grant No. P30CA008748; MSK), a grant of the Ministry of Health of the Czech Republic (NV15-29959A), Charles University projects PROGRES Q28/LF1 and SVV2019/260367, an HIR Grant UM.C/HlR/MOHE/06 from the Ministry of Higher Education, Malaysia, and the National Health and Medical Research Council, Australia (NHMRC, Project Grant APP1029974). kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. W.D.F. was funded in part by Susan G Komen. A.L. was supported by the China Scholarship Council. T.N.-D. is an Early Career Fellow of the National Breast Cancer Foundation and M.S. is a NHMRC Senior Research Fellow of the National Health and Medical Research Council. M.T. was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Addenbrooke's Hospital and European Union Seventh Framework Program (2007-2013)/European Research Council (310018). S.P. was supported by the Swiss National Science Foundation (Ambizione grant number: PZ00P3_168165). J.S.R-F. is partly funded by the Breast Cancer Research Foundation and Britta Weigelt by Cycle for Survival.