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BRCA1/2 Pathogenic Variants Are Not Common in Merkel Cell Carcinoma: Comprehensive Molecular Study of 30 Cases and Meta-Analysis of the Literature.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2023 Jul; Vol. 143 (7), pp. 1178-1186. Date of Electronic Publication: 2023 Feb 07. - Publication Year :
- 2023
-
Abstract
- Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer. Management of advanced MCC is mainly based on immune-checkpoint inhibitors. The high failure rate warrants an investigation of new therapeutic targets. The recent identification of BRCA1 or BRCA2 (BRCA1/2) mutations in some MCC raises the issue of the use of poly-(ADP-Ribose)-polymerase inhibitors in selected advanced cases. The main objective of our study is to determine the accurate frequency of BRCA1/2 pathogenic variants. We studied a series of 30 MCC and performed a meta-analysis of BRCA1/2 variants of published cases in the literature. In our series, we detected only one BRCA2 pathogenic variant. The low frequency of BRCA1/2 pathogenic variants in our series of MCC (3%) was confirmed by the meta-analysis of BRCA1/2 variants in the literature. Among the 915 MCC from 13 published series studied for molecular alterations of BRCA1/2, only 12 BRCA1/2 pathogenic mutations were identified (1-2% of MCC), whereas many other BRCA1/2 variants were variants of unknown significance or benign. BRCA1/2 pathogenic variants are uncommon in MCC. However, in BRCA-mutated MCC, poly-(ADP-Ribose)-polymerase inhibitors might be a valuable therapeutic option requiring validation by clinical trials.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Female
BRCA1 Protein genetics
BRCA2 Protein genetics
Poly(ADP-ribose) Polymerase Inhibitors therapeutic use
Adenosine Diphosphate Ribose therapeutic use
Germ-Line Mutation
Genetic Predisposition to Disease
Carcinoma, Merkel Cell genetics
Carcinoma, Merkel Cell drug therapy
Skin Neoplasms drug therapy
Skin Neoplasms genetics
Ovarian Neoplasms drug therapy
Ovarian Neoplasms genetics
Ovarian Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 143
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 36754117
- Full Text :
- https://doi.org/10.1016/j.jid.2023.01.014