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.

BRCA1 Protein / genetics Breast Neoplasms / diagnosis Female Genetic Predisposition to Disease Genetic Testing Humans Ovarian Neoplasms / diagnosis Pancreatic Neoplasms / diagnosis
breast cancer germline pathogenic variants multi-gene panel testing ovarian cancer pancreatic cancer

Journal

ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685

Informations de publication

Date de publication:
08 2021
Historique:
received: 03 03 2021
revised: 11 06 2021
accepted: 14 07 2021
pubmed: 10 8 2021
medline: 30 10 2021
entrez: 9 8 2021
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1016/j.esmoop.2021.100235 PMID: 34371384 PMC: PMC8358413
pubmed: 34371384
pii: S2059-7029(21)00196-4
doi: 10.1016/j.esmoop.2021.100235
pmc: PMC8358413
pii:
doi:

Substances chimiques

BRCA1 Protein 0
BRCA1 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

100235

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure The authors have declared no conflicts of interest.

Auteurs

M Bono (M)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

D Fanale (D)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

L Incorvaia (L)

Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Medical Oncology, University of Palermo, Palermo, Italy.

D Cancelliere (D)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

A Fiorino (A)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

V Calò (V)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

A Dimino (A)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

C Filorizzo (C)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

L R Corsini (LR)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

C Brando (C)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

G Madonia (G)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

A Cucinella (A)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

R Scalia (R)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

N Barraco (N)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

F Guadagni (F)

BioBIM (Interinstitutional Multidisciplinary Biobank), IRCCS San Raffaele Pisana, Rome, Italy; Department of Human Sciences & Quality of Life Promotion, San Raffaele Roma Open University, Rome, Italy.

E Pedone (E)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

G Badalamenti (G)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.

A Russo (A)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy. Electronic address: antonio.russo@usa.net.

V Bazan (V)

Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Section of Medical Oncology, University of Palermo, Palermo, Italy.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéine BRCA1 › Impact of deleterious variants in other genes...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Impact of deleterious variants in other genes...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Impact of deleterious variants in other genes...
questionsmedicales.fr › Établissements, main d'oeuvre et services de soins de santé › Services de santé › Services de médecine préventive › Services de diagnostic › Dépistage génétique › Impact of deleterious variants in other genes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Impact of deleterious variants in other genes...
questionsmedicales.fr › Maladies endocriniennes › Troubles gonadiques › Maladies ovariennes › Tumeurs de l'ovaire › Impact of deleterious variants in other genes...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Impact of deleterious variants in other genes...