Association of ATM and ARID1A in gastric carcinoma

• Published in: Pathology, research and practice research and practice, 2024-11, Vol.263, p.155664, Article 155664
• Main Authors: Hwang, Inwoo, Lee, Somin, Kim, Yuyeon, Kim, Deok Geun, Kang, So Young, Ahn, Soomin, Lee, Jeeyun, Kim, Kyoung-Mee
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; ARID1A; Ataxia Telangiectasia Mutated Proteins - genetics; ATM; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Expression; Female; Gastric carcinoma; Humans; Immunohistochemistry; Male; Middle Aged; Mutation; Next-generation sequencing; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Transcription Factors - genetics
• ISSN: 0344-0338; 1618-0631; 1618-0631
• DOI: 10.1016/j.prp.2024.155664

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. 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. 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