ArticleNPJ precision oncology2024
Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting.
Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 8 citations in OpenAlex.
- Adjuvant nivolumab in muscle-invasive urothelial carcinoma: exploratory biomarker analysis of the randomized phase 3 CheckMate 274 trial.Nature medicine · 2025Trial
- Gastric Epithelium from BRCA1 and BRCA2 Carriers Harbors Increased Double-Stranded DNA Damage and Enhanced Growth Potential.Molecular cancer research : MCR · 2026Article
- The Role of Homologous Recombination Deficiency (HRD) in Renal Cell Carcinoma (RCC): Biology, Biomarkers, and Therapeutic Opportunities.Current oncology (Toronto, Ont.) · 2025Review
- Chemotherapy-associated mutational process signature and genomic alterations associated with outcome in metastatic pancreatic cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Predictive value of homologous recombination-related gene mutations in survival outcomes of first-line nivolumab plus chemotherapy for gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Gastric epithelium frombioRxiv : the preprint server for biology · 2025Article
- PARP inhibitors in gastric cancer: unlocking precision oncology.The oncologist · 2025Review
- Review
- Joint inference of mutational signatures from indels and single-nucleotide substitutions reveals prognostic impact of DNA repair deficiencies.Genome medicine · 2025Article
- Harnessing the gut microbiome to modulate ferroptosis: a metabolic strategy for the treatment of digestive tract cancers.Frontiers in immunology · 2025Review
- Distinct genomic features and mutational signatures of nucleotide excision repair and mismatch repair in thymoma.American journal of cancer research · 2025Article
- Landscape of homologous recombination deficiency in gastric cancer and clinical implications for first-line chemotherapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
23 authors at 12 institutions in 4 countries.
Funding
Abstract
Homologous recombination (HR) and nucleotide excision repair (NER) are the two most frequently disabled DNA repair pathways in cancer. HR-deficient breast, ovarian, pancreatic and prostate cancers respond well to platinum chemotherapy and PARP inhibitors. However, the frequency of HR deficiency in gastric and esophageal adenocarcinoma (GEA) still lacks diagnostic and functional validation. Using whole exome and genome sequencing data, we found that a significant subset of GEA, but very few colorectal adenocarcinomas, show evidence of HR deficiency by mutational signature analysis (HRD score). High HRD gastric cancer cell lines demonstrated functional HR deficiency by RAD51 foci assay and increased sensitivity to platinum chemotherapy and PARP inhibitors. Of clinical relevance, analysis of three different GEA patient cohorts demonstrated that platinum treated HR deficient cancers had better outcomes. A gastric cancer cell line with strong sensitivity to cisplatin showed HR proficiency but exhibited NER deficiency by two photoproduct repair assays. Single-cell RNA-sequencing revealed that, in addition to inducing apoptosis, cisplatin treatment triggered ferroptosis in a NER-deficient gastric cancer, validated by intracellular GSH assay. Overall, our study provides preclinical evidence that a subset of GEAs harbor genomic features of HR and NER deficiency and may therefore benefit from platinum chemotherapy and PARP inhibitors.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.