ARID2

Overview

ARID2 (AT-Rich Interaction Domain 2) is a subunit of the PBAF (polybromo BRG1-associated factor) SWI/SNF chromatin remodeling complex. As a tumor suppressor, loss-of-function mutations in ARID2 are observed in multiple cancer types. In the corpus, ARID2 mutations have been identified in melanocytes from indoor tanning bed users, in the actinic keratosis-to-cutaneous squamous cell carcinoma (cSCC) evolutionary transition, and in gynecologic cancers under nivolumab treatment.

Alterations observed in the corpus

  • ARID2 T408I mutation found alongside NF1 co-mutation in a melanocyte from a tanning cohort donor in a molecular study of indoor tanning effects (182 melanocytes from 26 donors) PMID:38895302.
  • ARID2 (along with CRTC1 and MAP3K1) among rare shared SNVs detected across four metastatic lesions of a single PDTO-profiled sarcoma patient (SARC0075); the CNV landscape across lesions was substantially discordant despite shared SNVs PMID:39305899.
  • ARID2 loss-of-function mutations enriched specifically at the actinic keratosis (AK)-to-cutaneous squamous cell carcinoma (cSCC) transition in a clonal evolution study of 16 AK-cSCC pairs; ARID2 loss was associated with SWI/SNF disruption and potential immune evasion PMID:39091884.
  • ARID2 (SWI/SNF complex member) mutated in dMMR/MSI-H gynecologic cancers treated with nivolumab with no significant difference in mutation rates between responders and non-responders (n=35) PMID:38653864.
  • ARID2 LOF mutations in 6% of GBC; structural variants in 2 samples PMID:36228155
  • ARID2 mutations identified in breast cancer WES of 100 tumors, further implicating SWI/SNF complex disruption in breast cancer PMID:22722201
  • ARID2 is recurrently mutated in melanoma among 121 tumors (Broad WES cohort), with mutations enriching in UV-signature contexts PMID:22817889
  • ARID2 is significantly mutated in a Yale melanoma WES cohort of 147 tumors, independently validating its role as a melanoma driver affecting the SWI/SNF complex PMID:22842228
  • Somatically mutated in pancreatic cancer (ICGC WES, 142 tumors); ARID2 loss-of-function mutations identified among significantly mutated genes in the SWI/SNF chromatin-remodeling complex PMID:23103869
  • Chromatin-remodeling SWI/SNF complex member mutated in EAC (esca_broad); part of the 24% of EACs with SWI/SNF alterations (including ARID1A, SMARCA4, PBRM1, JARID2) PMID:23525077
  • Mutated SWI/SNF complex member in ESCC; identified as significantly mutated in 139 paired ESCC tumor/germline samples PMID:24686850
  • Chromatin remodeling driver identified by NGS in HCC; listed among the newly identified HCC driver genes alongside ARID1A PMID:24735922
  • Loss-of-function mutation in 7% (range 3–10%) of HCCs (WES, n=1,289); chromatin-modifier trunk driver classified as non-actionable PMID:24798001
  • Chromatin remodeler truncated or hit at COSMIC sites in cutaneous squamous cell carcinoma; part of SWI/SNF complex alterations observed in 48% of 29-tumor cSCC cohort PMID:25589618
  • Chromatin-remodeling gene recurrently mutated in HCC; SWI/SNF pathway altered in 28% of 243 HCC tumors; SMARCA2 alteration enriched in alcohol-related HCC PMID:25822088
  • SMG strongly enriched in melanoma CIMP cluster (OR=3.5, p=0.0003); frequently co-occurs with NF1 — proposed synthetic-lethal vulnerability for chromatin-modifier targeting PMID:26091043
  • Inactivating mutations in the SWI/SNF complex in desmoplastic melanoma; co-occurs with ARID1A inactivation; both confirmed as tumor-suppressor gene alterations PMID:26343386
  • One of the most frequent SWI/SNF chromatin-remodelling alterations in periampullary adenocarcinomas (AMPAC, DUOAC, CAC); equally distributed across the three tumour types PMID:26804919
  • Newly nominated glioma driver (n=20 mutations) in a pan-glioma WGS/WES cohort of 1,122 diffuse gliomas; classified as a chromatin-modification gene PMID:26824661
  • ARID2, as part of the SWI/SNF complex, mutated in 36% ATC vs 6% PDTC (P = 1×10⁻⁴) in a 341-gene targeted sequencing cohort (n=117 advanced thyroid tumors); mutations generally mutually exclusive within the complex PMID:26878173
  • Inactivating mutations identified in lung adenocarcinoma by pan-lung WES (TCGA); part of the SWI/SNF chromatin-remodeling complex altered in NSCLC PMID:27158780
  • ARID2 among the most frequently mutated epigenetic modifiers in DUX4/ERG B-ALL (epigenetic-modifier mutations present in 56.3% of cases overall) PMID:27776115
  • ARID2 is a SWI/SNF subunit mutated in medulloblastoma; together with SMARCA4 and ARID1A, SWI/SNF subunits are altered in 33% of WNT MBs, providing rationale for PRC2 inhibitors (trial NCT02601937) PMID:28726821
  • ARID2 cited as an essential PBAF-complex component whose loss (in mouse models) sensitizes tumor cells to T-cell-mediated killing, supporting a PBAF-wide immune-priming mechanism in ccRCC PMID:29301960.
  • ARID2 is a SWI/SNF member altered in ~5% of 1,013 prostate cancers (prad_p1000), enriched in ETS-fusion-negative tumors alongside ARID1A, ARID4A, and SMARCA1. PMID:29610475

Cancer types (linked)

  • MEL — ARID2 mutations identified in premalignant melanocytes of tanning bed users PMID:38895302.
  • CSCC — ARID2 loss-of-function is a late event marking the AK-to-cSCC transition, potentially linked to immune evasion via SWI/SNF disruption PMID:39091884.
  • UCEC — ARID2 alterations present in dMMR/MSI-H endometrial and ovarian cancers; not associated with nivolumab response PMID:38653864.

Co-occurrence and mutual exclusivity

  • In melanocytes, ARID2 T408I co-occurred with NF1 loss-of-function in the same cell, suggesting convergent MAPK pathway and SWI/SNF disruption PMID:38895302.
  • In cSCC evolution, ARID2 loss occurs after TP53/NOTCH1 truncal mutations and CDKN2A/TERT AK-stage events, placing it as a late driver in a stepwise model PMID:39091884.

Therapeutic relevance

  • ARID2 loss at the AK-cSCC transition may promote immune evasion, providing mechanistic support for immune checkpoint inhibitor therapy in advanced cSCC PMID:39091884.

Open questions

  • Whether SWI/SNF complex mutations (ARID2) directly drive immune evasion at the AK-to-cSCC transition, as suggested by emerging evidence from other tumor types, requires direct experimental validation PMID:39091884.
  • Why ARID2 mutations do not predict nivolumab response in dMMR gynecologic cancers, despite SWI/SNF disruption being theoretically linked to immune recognition, is unresolved PMID:38653864.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36228155

This page was processed by crosslinker on 2026-05-14. - PMID:22722201

This page was processed by crosslinker on 2026-05-14. - PMID:22817889

This page was processed by crosslinker on 2026-05-14. - PMID:22842228

This page was processed by crosslinker on 2026-05-14. - PMID:23103869

This page was processed by crosslinker on 2026-05-14. - PMID:23525077

This page was processed by crosslinker on 2026-05-14. - PMID:24686850

This page was processed by crosslinker on 2026-05-14. - PMID:24735922

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:25822088

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:26343386

This page was processed by crosslinker on 2026-05-14. - PMID:26804919

This page was processed by entity-page-writer on 2026-05-15. - PMID:26824661

This page was processed by entity-page-writer on 2026-05-15. - PMID:26878173

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15. - PMID:29301960

This page was processed by wiki-cli on 2026-05-15. - PMID:29610475

This page was processed by wiki-cli on 2026-05-15.