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Soo Park, MD
Soo Park, MD
Posted: Friday, April 29, 2022
Although cytotoxic chemotherapy and checkpoint inhibitors have shown some utility in treating Merkel cell carcinoma, there is currently no standard of care for targeted therapy. Thus, Danielle Brazel, MD, of the University of California, Irvine, and colleagues examined the presence of potentially targetable gene alterations in patients with Merkel cell carcinoma who were catalogued in the American Association for Cancer Research (AACR) GENIE database. The results, which were presented at the AACR Annual Meeting 2022 (Abstract 1185/15), reflected that many patients had similar mutations in cancer-linked signaling pathways, which may potentially serve as therapeutic targets in the future.
The investigators analyzed patient tumor data from both primary tumors (54%) and metastases (42.4%), specifically examining demographic data, gene alterations annotated by OncoKB, and alterations in Cancer Genome Atlas (TCGA) pan-cancer pathways. A total of 295 patients with Merkel cell carcinoma, 34.6% of whom were female, were included in the analysis.
Reportedly, the median number of alterations was three (standard deviation = 21.4, range = 0–178), with 17.4% of the total 3,799 identified alterations specified as oncogenic. Separately, 18.5% of patient samples had a OncoKB evidence Level 1 to 3 mutation, and an additional 13.9% had a Level 4 (potential biomarker) mutation. The most frequent Level 3B mutations included PIK3CA (4.1%) and BRCA1/2 (4.1%). As for Level 4 mutations, PTEN (4.4%) and ARID1A (3.7%) were among the most frequent. Moreover, 60.7% of cases showed alterations in TCGA pan-cancer pathways, and 28.5% had alterations in multiple pathways. The RTK-RAS (37.6%), TP53 (33.9%), and cell-cycle (33.9%) pathways were among the most commonly altered. Additionally, 7.5% of patients had mutations in DNA damage repair genes, including BRCA1/2, CHEK1/2, and RAD51.
Only three gene fusions were identified—ATM–CDK12 and TSC2, along with PTEN. Copy number alterations were identified in a small number of patients.
Disclosure: The study authors reported no conflicts of interest.
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