Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

ESMO Open

article

M. Bono¹  D. Fanale¹  L. Incorvaia²  D. Cancelliere¹  A. Fiorino¹  V. Calò¹  A. Dimino¹  C. Filorizzo¹  L.R. Corsini¹  C. Brando¹  G. Madonia¹  A. Cucinella¹  R. Scalia¹  N. Barraco¹  F. Guadagni³  E. Pedone¹  G. Badalamenti¹  A. Russo¹  V. Bazan² 

[1] Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo;Department of Biomedicine, Neuroscience and Advanced Diagnostics ,(Bi.N.D.), Section of Medical Oncology, University of Palermo;BioBIM ,(Interinstitutional Multidisciplinary Biobank);Department of Human Sciences & Quality of Life Promotion, San Raffaele Roma Open University

关键词: breast cancer;    germline pathogenic variants;    multi-gene panel testing;    ovarian cancer;    pancreatic cancer;   

DOI  :  10.1016/j.esmoop.2021.100235

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes.Patients and methods Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relatives. For this purpose, 205 out of 915 BC, OC, or PC patients, resulted negative for BRCA1/2 and with significant personal and/or family history of cancer, were genetically tested for germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes different from BRCA1/2.Results Our investigation revealed that 31 (15.1%) out of 205 patients harboured germline PVs/LPVs in no-BRCA genes, including PALB2, CHEK2, ATM, MUTYH, MSH2, and RAD51C. Interestingly, in the absence of an analysis conducted through multi-gene panel, a considerable percentage (15.1%) of PVs/LPVs would have been lost.Conclusions Providing a multi-gene panel testing to BRCA1/2-wt BC/OC/PC patients with a strong personal and/or family history of cancer could significantly increase the detection rates of germline PVs/LPVs in other cancer predisposition genes beyond BRCA1/2. The use of a multi-gene panel testing could improve the inherited cancer risk estimation and clinical management of patients and unaffected family members.

【 授权许可】

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