Association of Homologous Recombination-DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers.
Mol Cancer Ther
; 21(1): 227-236, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34725190
ABSTRACT
The prevalence of homologous recombination-DNA damage response (HR-DDR) genetic alterations is of therapeutic interest in gastroesophageal cancers. This study is a comprehensive assessment of HR-DDR mutation prevalence across gastroesophageal adenocarcinomas and squamous cell carcinomas. Here we investigate the association of HR-DDR mutations with known predictors for immune-checkpoint inhibition [deficiency in mismatch-repair (dMMRP), tumor mutational burden (TMB), and programmed death ligand 1 (PD-L1)]. We confirmed HR-DDR mutations are present in a subset of gastroesophageal adenocarcinomas (23%) and gastroesophageal squamous cell carcinomas (20%). Biomarker expression of dMMRP (18% vs. 1%) and TMB-high with a cutoff of ≥10 mt/MB (27% vs. 9%) was significantly more prevalent in the DDR-mutated cohort compared with the non-DDR-mutated cohort. Mean combined positive score for PD-L1 in the total adenocarcinoma cohort was significantly higher in the DDR-mutated cohort compared with the non-DDR-mutated cohort (10.1 vs. 5.8). We demonstrated that alterations in ARID1A, BRCA2, PTEN, and ATM are correlated with dMMRP, TMB-high, and increased PD-L1 expression in gastroesophageal adenocarcinomas. Our findings show that a subset of gastroesophageal tumors harbor HR-DDR mutations correlated with established immune biomarkers. By better understanding the relationship between HR-DDR mutations and immune biomarkers, we may be able to develop better immunotherapy combination strategies to target these tumors.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Dano ao DNA
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Neoplasias Esofágicas
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Biomarcadores Tumorais
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Sequenciamento de Nucleotídeos em Larga Escala
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Recombinação Homóloga
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article