1. ARID2 mutations may relay a distinct subset of cutaneous melanoma patients with different outcomes.
- Author
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Akinjiyan, Favour, Nassief, George, Phillipps, Jordan, Adeyelu, Tolulope, Elliott, Andrew, Abdulla, Farah, Zhou, Alice, Souroullas, George, Kim, Kevin, Vanderwalde, Ari, Park, Soo, and Ansstas, George
- Subjects
Humans ,Melanoma ,B7-H1 Antigen ,Skin Neoplasms ,Mutation ,Kaplan-Meier Estimate ,Biomarkers ,Tumor ,Transcription Factors - Abstract
ARID genes encode subunits of SWI/SNF chromatin remodeling complexes and are frequently mutated in human cancers. We investigated the correlation between ARID mutations, molecular features, and clinical outcomes in melanoma patients. Cutaneous melanoma samples (n = 1577) were analyzed by next-generation sequencing. Samples were stratified by pathogenic/likely pathogenic mutation in ARID genes (ARID1A/2/1B/5B). PD-L1 expression was assessed using IHC (SP142; positive (+): ≥ 1%). Tumor mutation burden (TMB)-high was defined as ≥ 10 mutations/Mb. Transcriptomic signatures predictive of response to immune checkpoint inhibitors-interferon gamma and T-cell inflamed score were calculated. Real-world overall survival (OS) information was obtained from insurance claims data, with Kaplan-Meier estimates calculated from time of tissue collection until last date of contact. Mann-Whitney U, Chi-square, and Fisher exact tests were applied where appropriate, with p values adjusted for multiple comparisons. ARID2 mutations were more prevalent in cutaneous melanoma compared to ARID1A (11.0%: n = 451 vs 2.8%: n = 113), with concurrent ARID1A/ARID2 mutation in 1.1% (n = 46) of samples. ARID mutations were associated with a high prevalence of RAS pathway mutations-NF1 (ARID1A, 52.6%; ARID2, 48.5%; ARID1A/2, 63.6%; and ARID-WT, 13.3%; p
- Published
- 2024