{"title":"Association of ATM and ARID1A in gastric carcinoma","authors":"","doi":"10.1016/j.prp.2024.155664","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The ataxia telangiectasia mutated (ATM) gene is involved in the repair of double-stranded DNA breaks and a component of the DNA damage repair pathway. Tumors with mutations or low expression of both <em>ARID1A</em> and <em>ATM</em> exhibit increased numbers of tumor-infiltrating lymphocytes and a favorable prognosis. However, the relationship between <em>ATM</em> and <em>ARID1A</em> in gastric carcinoma (GC) is unclear.</div></div><div><h3>Methods</h3><div>We used the mRNA expression data from the Asian Cancer Research Group to construct tissue microarrays (<em>N</em> = 249). Next-generation sequencing (NGS) databases of Samsung Medical Center (SMC) (<em>N</em> = 813) were used to compare genetic alterations. Tissue microarrays were used for ATM and ARID1A immunohistochemistry, and expressions were categorized as “low” and “high.” NGS data from TCGA-STAD (<em>N</em> = 431) were used as independent cohorts for genetic alterations validation.</div></div><div><h3>Results</h3><div>In GCs, 32.1 % (80/249) of the cases showed low ATM protein expression (ATM<sup>low</sup>) and 20.9 % (52/249) showed low ARID1A expression (ARID1A<sup>low</sup>). ATM<sup>low</sup> was significantly associated with older age (<em>P</em> <.01), gross type of tumor (<em>P</em> =.02), histology (<em>P</em> <. 01), lower incidence of perineural invasion (<em>P</em> =.04), lower disease stage (<em>P</em> <.01), microsatellite instability-high (<em>P</em> <.01), and ARID1A<sup>low</sup> (<em>P</em> <.01). Furthermore, GCs in the SMC NGS database showed that <em>ATM</em> mutations were significantly correlated with <em>ARID1A</em> mutations (<em>P</em> <.01), and this finding remained significant in TCGA-STAD validation cohort (<em>P</em> <.01).</div></div><div><h3>Conclusion</h3><div>ATM<sup>low</sup> in GCs shows a characteristic clinicopathological feature that correlates strongly with ARID1A<sup>low</sup>. <em>ATM</em> mutation was also associated with <em>ARID1A</em> mutations, highlighting the interactions between <em>ATM</em> and <em>ARID1A</em> in GC and suggesting a potential therapeutic target.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathology, research and practice","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0344033824005752","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
The ataxia telangiectasia mutated (ATM) gene is involved in the repair of double-stranded DNA breaks and a component of the DNA damage repair pathway. Tumors with mutations or low expression of both ARID1A and ATM exhibit increased numbers of tumor-infiltrating lymphocytes and a favorable prognosis. However, the relationship between ATM and ARID1A in gastric carcinoma (GC) is unclear.
Methods
We used the mRNA expression data from the Asian Cancer Research Group to construct tissue microarrays (N = 249). Next-generation sequencing (NGS) databases of Samsung Medical Center (SMC) (N = 813) were used to compare genetic alterations. Tissue microarrays were used for ATM and ARID1A immunohistochemistry, and expressions were categorized as “low” and “high.” NGS data from TCGA-STAD (N = 431) were used as independent cohorts for genetic alterations validation.
Results
In GCs, 32.1 % (80/249) of the cases showed low ATM protein expression (ATMlow) and 20.9 % (52/249) showed low ARID1A expression (ARID1Alow). ATMlow was significantly associated with older age (P <.01), gross type of tumor (P =.02), histology (P <. 01), lower incidence of perineural invasion (P =.04), lower disease stage (P <.01), microsatellite instability-high (P <.01), and ARID1Alow (P <.01). Furthermore, GCs in the SMC NGS database showed that ATM mutations were significantly correlated with ARID1A mutations (P <.01), and this finding remained significant in TCGA-STAD validation cohort (P <.01).
Conclusion
ATMlow in GCs shows a characteristic clinicopathological feature that correlates strongly with ARID1Alow. ATM mutation was also associated with ARID1A mutations, highlighting the interactions between ATM and ARID1A in GC and suggesting a potential therapeutic target.
期刊介绍:
Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.