Department of Pathology and Molecular Oncology, Central Laboratory of Pathology, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France.
Biologie des infections à polyomavirus team, UMR INRA ISP 1282, University of Tours, Tours, France; Department of Pathology, Centre Hospitalier Universitaire de Tours, Tours, France.
J Invest Dermatol. 2023 Jul;143(7):1178-1186. doi: 10.1016/j.jid.2023.01.014. Epub 2023 Feb 7.
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.
默克尔细胞癌（Merkel cell carcinoma，MCC）是一种罕见且侵袭性强的皮肤神经内分泌癌。晚期 MCC 的治疗主要基于免疫检查点抑制剂。高失败率需要探索新的治疗靶点。最近在一些 MCC 中发现了 BRCA1 或 BRCA2（BRCA1/2）突变，这引发了在某些晚期病例中使用聚（ADP-核糖）聚合酶抑制剂的问题。我们研究的主要目的是确定 BRCA1/2 致病变体的准确频率。我们研究了 30 例 MCC，并对文献中已发表的 BRCA1/2 变体进行了荟萃分析。在我们的系列中，仅检测到一个 BRCA2 致病变体。通过对文献中 BRCA1/2 变体的荟萃分析，证实了我们的 MCC 系列中 BRCA1/2 致病变体的低频率（3%）。在对 BRCA1/2 分子改变进行研究的 13 个已发表系列的 915 例 MCC 中，仅鉴定出 12 种 BRCA1/2 致病突变（占 MCC 的 1-2%），而许多其他 BRCA1/2 变体则为意义不明或良性的变体。BRCA1/2 致病变体在 MCC 中并不常见。然而，在 BRCA 突变型 MCC 中，聚（ADP-核糖）聚合酶抑制剂可能是一种有价值的治疗选择，需要通过临床试验进行验证。
