Subtopic Deep Dive

ARID1A Mutations in Oncogenic Transformation
Research Guide

What is ARID1A Mutations in Oncogenic Transformation?

ARID1A mutations are loss-of-function alterations in the SWI/SNF chromatin remodeling complex subunit that drive oncogenic transformation in gynecologic cancers through enhancer dysregulation.

ARID1A (BAF250A) promotes SWI/SNF complex formation and is frequently mutated in ovarian clear cell and endometrioid cancers (Guan et al., 2011, 443 citations). These mutations disrupt chromatin remodeling, leading to aberrant gene expression in transformation (Shain and Pollack, 2013, 559 citations). Studies across cancers like breast and lung confirm ARID1A as a tumor suppressor (Stephens et al., 2012, 1707 citations; Seo et al., 2012, 586 citations).

Curated Papers

Key Challenges

Why It Matters

ARID1A mutations occur in 50-60% of ovarian clear cell carcinomas, enabling precision oncology targeting of synthetic lethal partners like ARID1B (Guan et al., 2011). In endometrial cancers, ARID1A loss cooperates with PIK3CA mutations to promote tumor progression, informing clinical trials (Shain and Pollack, 2013). SWI/SNF disruptions, including ARID1A, affect 20% of human malignancies, guiding immunotherapy responses (Hodges et al., 2016). These insights drive biomarker development in gynecologic cancers (Masliah-Planchon et al., 2014).

Key Research Challenges

Mechanisms of enhancer dysregulation

ARID1A loss impairs SWI/SNF maintenance of lineage-specific enhancers, but exact transformation pathways remain unclear (Alver et al., 2017). Studies link it to Myc regulation in leukemia, yet gynecologic contexts differ (Shi et al., 2013). Functional validation requires advanced models.

Tissue-specific mutation effects

ARID1A mutations predominate in ovarian cancers but vary across breast and lung, complicating universal models (Stephens et al., 2012; Seo et al., 2012). SWI/SNF subunit interplay differs by cancer type (Shain and Pollack, 2013). Integrating multi-omics data is needed.

Therapeutic targeting vulnerabilities

SWI/SNF-deficient tumors show synthetic lethality, but clinical translation lags (Hodges et al., 2016). Enhancer rewiring post-ARID1A loss resists standard therapies (Hargreaves and Crabtree, 2011). CRISPR screens are essential for partner identification.

Essential Papers

The landscape of cancer genes and mutational processes in breast cancer

Philip J. Stephens, Patrick Tarpey, Helen Davies et al. · 2012 · Nature · 1.7K citations

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the rema...

The whole-genome landscape of medulloblastoma subtypes

Paul A. Northcott, Ivo Buchhalter, A. Sorana Morrissy et al. · 2017 · Nature · 1.1K citations

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments wit...

ATP-dependent chromatin remodeling: genetics, genomics and mechanisms

Diana C. Hargreaves, Robert H. Crabtree · 2011 · Cell Research · 896 citations

The transcriptional landscape and mutational profile of lung adenocarcinoma

Jeong‐Sun Seo, Young Seok Ju, Won‐Chul Lee et al. · 2012 · Genome Research · 586 citations

All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the...

The Spectrum of SWI/SNF Mutations, Ubiquitous in Human Cancers

A. Hunter Shain, Jonathan R. Pollack · 2013 · PLoS ONE · 559 citations

SWI/SNF is a multi-subunit chromatin remodeling complex that uses the energy of ATP hydrolysis to reposition nucleosomes, thereby modulating gene expression. Accumulating evidence suggests that SWI...

Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated <i>Myc</i> regulation

Junwei Shi, Warren A. Whyte, Cinthya Zepeda‐Mendoza et al. · 2013 · Genes & Development · 448 citations

Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for...

<i>ARID1A</i> , a Factor That Promotes Formation of SWI/SNF-Mediated Chromatin Remodeling, Is a Tumor Suppressor in Gynecologic Cancers

Bin Guan, Tian‐Li Wang, Ie‐Ming Shih · 2011 · Cancer Research · 443 citations

Abstract ARID1A (BAF250A) promotes the formation of SWI/SNF chromatin remodeling complexes containing BRG1 or BRM. It has emerged as a candidate tumor suppressor based on its frequent mutations in ...

Reading Guide

Foundational Papers

Start with Guan et al. (2011) for ARID1A's role in gynecologic SWI/SNF complexes, then Shain and Pollack (2013) for mutation spectrum, and Hargreaves and Crabtree (2011) for chromatin mechanisms.

Recent Advances

Study Hodges et al. (2016) for BAF/PBAF roles in cancer and Alver et al. (2017) for enhancer maintenance defects.

Core Methods

Core techniques include whole-genome sequencing (Stephens et al., 2012), CRISPR knockouts for transformation assays (Shi et al., 2013), and ChIP-seq for enhancer mapping (Hargreaves and Crabtree, 2011).

How PapersFlow Helps You Research ARID1A Mutations in Oncogenic Transformation

Discover & Search

PapersFlow's Research Agent uses searchPapers and citationGraph to map ARID1A mutation landscapes, starting from Guan et al. (2011) to find 50+ SWI/SNF papers. exaSearch uncovers enhancer-focused studies beyond OpenAlex, while findSimilarPapers links Shain and Pollack (2013) to gynecologic contexts.

Analyze & Verify

Analysis Agent applies readPaperContent to extract mutation frequencies from Stephens et al. (2012), then verifyResponse with CoVe checks claims against 10 related papers. runPythonAnalysis performs statistical verification of citation overlaps in SWI/SNF cancers, with GRADE scoring evidence strength for ARID1A tumor suppression.

Synthesize & Write

Synthesis Agent detects gaps in enhancer transformation mechanisms post-ARID1A loss, flagging contradictions between leukemia (Shi et al., 2013) and ovarian models. Writing Agent uses latexEditText, latexSyncCitations for Guan et al. (2011), and latexCompile to generate review sections, with exportMermaid for chromatin remodeling pathway diagrams.

Use Cases

"Analyze mutation frequencies of ARID1A across ovarian vs breast cancer cohorts from Stephens and Guan papers"

Research Agent → searchPapers('ARID1A mutations ovarian breast') → Analysis Agent → readPaperContent(Stephens 2012 + Guan 2011) → runPythonAnalysis(pandas aggregation of mutation rates) → CSV export of stats table.

"Write LaTeX section on ARID1A loss in SWI/SNF complex with citations to foundational papers"

Synthesis Agent → gap detection(Shain 2013, Hodges 2016) → Writing Agent → latexEditText('ARID1A section draft') → latexSyncCitations(Guan 2011 et al.) → latexCompile → PDF output with figure.

"Find GitHub repos with CRISPR models for ARID1A knockout in cancer cell lines"

Research Agent → paperExtractUrls(Alver 2017) → paperFindGithubRepo → Code Discovery → githubRepoInspect(CRISPR ARID1A) → Python sandbox verification of transformation assays.

Automated Workflows

Deep Research workflow conducts systematic review of 50+ ARID1A/SWI/SNF papers: searchPapers → citationGraph → GRADE all abstracts → structured report on oncogenic roles. DeepScan applies 7-step analysis to Guan et al. (2011): readPaperContent → CoVe verification → runPythonAnalysis on mutation data → checkpoint critique. Theorizer generates hypotheses on ARID1A-enhancer synthetic lethality from Shi et al. (2013) and Hodges et al. (2016).

Try Doxa for ARID1A Mutations in Oncogenic Transformation Research

Frequently Asked Questions

What defines ARID1A mutations in oncogenic transformation?

ARID1A loss-of-function mutations disrupt SWI/SNF chromatin remodeling, promoting enhancer dysregulation in ovarian and endometrial cancers (Guan et al., 2011; Shain and Pollack, 2013).

What methods study ARID1A mutations?

Whole-genome sequencing identifies drivers (Stephens et al., 2012), CRISPR models test transformation (Alver et al., 2017), and ChIP-seq maps enhancer changes (Hargreaves and Crabtree, 2011).

What are key papers on ARID1A in cancer?

Guan et al. (2011, Cancer Research, 443 citations) establishes ARID1A as a gynecologic tumor suppressor; Shain and Pollack (2013, PLoS ONE, 559 citations) catalogs SWI/SNF mutations across cancers.

What open problems exist in ARID1A research?

Unresolved issues include tissue-specific transformation mechanisms and therapeutic synthetic lethals beyond ARID1B, requiring multi-omics integration (Hodges et al., 2016; Masliah-Planchon et al., 2014).