The following is a summary of “BRCA1/2 Pathogenic Variants Are Not Common in Merkel Cell Carcinoma: Comprehensive Molecular Study of 30 Cases and Meta-Analysis of the Literature,” published in the July 2023 issue of Investigative Dermatology by Gaubert et al.

Merkel cell carcinoma (MCC) is an uncommon, aggressive cutaneous neuroendocrine cancer. Immune checkpoint inhibitors are the primary treatment option for advanced MCC. The high failure rate necessitates research into new therapeutic targets. The recent identification of BRCA1 or BRCA2 (BRCA1/2) mutations in certain advanced cases of MCC poses the question of using poly-(ADP-Ribose)-polymerase inhibitors. 

The researchers’ primary objective is to ascertain the precise frequency of BRCA1/2 pathogenic variants. The researchers analyzed a series of 30 cases of MCC and conducted a meta-analysis of BRCA1/2 variants from published cases. In their series, only one BRCA2 pathogenic variant was detected. The meta-analysis of BRCA1/2 variants in the scientific literature confirmed the low frequency (3%) of BRCA1/2 pathogenic variants in their series of MCC. 

Only 12 BRCA1/2 pathogenic mutations (12% of MCC) were identified among the 915 MCC from 13 published series analyzed for molecular alterations of BRCA1/2. In contrast, most other BRCA1/2 variants were variants of unknown significance or benign. In MCC, pathogenic BRCA1/2 variants are uncommon. In BRCA-mutated MCC, however, poly-(ADP-Ribose)-polymerase inhibitors may be a valuable therapeutic option requiring clinical validation trials.

Source: sciencedirect.com/science/article/pii/S0022202X23000684