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Status |
Public on Aug 06, 2022 |
Title |
BRCAness and Merkel cell carcinoma: Comprehensive molecular study of 35 cases and meta-analysis of the literature |
Organism |
Homo sapiens |
Experiment type |
Genome variation profiling by SNP array SNP genotyping by SNP array
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Summary |
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer. Management of advanced MCC is mainly based on immune-checkpoint inhibitors (ICI). The high failure rate (up to 75%) warrants 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 (PARPi) in selected advanced cases. The main objective of our study is to determine the accurate frequency of BRCA1/2 pathogenic variants. We studied a novel series of 35 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 (nonsense mutation; ENIGMA class 5) and one BRCA2 variant of unknown significance (VUS). The low frequency of BRCA1/2 pathogenic variants in our series of MCC (3%) was confirmed by the meta-analysis of BRCA1/2 variants of the literature. Among the 204 MCC studied for molecular alterations of BRCA1/2, only two BRCA1 pathogenic nonsense mutations were identified (1%), while the vast majority of BRCA1/2 variants were missense mutations classified as VUS. BRCA1/2 pathogenic variants are uncommon in MCC. However, in BRCA-mutated-MCC, PARPi might be a valuable therapeutic option requiring validation by clinical trials.
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Overall design |
Merkel cell carcinoma
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Contributor(s) |
Dadone-Montaudié B, Pedeutour F, Kubiniek V, Fabas T, Gaubert A, Kervarrec T, Montaudié H, Burel-Vandenbos F, Cardot-Leccia N, Di Mauro I, Tallet A |
Citation missing |
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Submission date |
Aug 05, 2022 |
Last update date |
Aug 08, 2022 |
Contact name |
Thibault FABAS |
Organization name |
CHU Nice
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Lab |
Génétiques des Tumeurs Solides
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Street address |
28 av Valombrose
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City |
NICE |
ZIP/Postal code |
06107 |
Country |
France |
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Platforms (1) |
GPL21558 |
[OncoScan_CNV] Affymetrix OncoScan CNV FFPE Assay |
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Samples (33)
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Relations |
BioProject |
PRJNA866483 |
Supplementary file |
Size |
Download |
File type/resource |
GSE210602_RAW.tar |
984.4 Mb |
(http)(custom) |
TAR (of CEL, OSCHP, TXT) |
Processed data provided as supplementary file |
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