ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Pan-cancer Analysis of Homologous Recombination Repair-associated Gene Alterations and Genome-wide Loss-of-Heterozygosity Score.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 78 citations in OpenAlex.
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- Olaparib maintenance versus placebo in platinum-sensitive non-small cell lung cancer: the Phase 2 randomized PIPSeN trial.British journal of cancer · 2024Trial
- The dual immune landscape of homologous recombination-deficient tumors: mechanisms and therapeutic implications.Cancer metastasis reviews · 2026Review
- Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.Targeted oncology · 2026Review
- Novel therapeutic strategies for metastatic castration‑resistant prostate cancer: Beyond androgen receptor pathway inhibition (Review).International journal of oncology · 2026Review
- Fanconi anemia complementation group C gene (FANCC) association with hereditary and sporadic renal tumors.The oncologist · 2026Article
- DNA damage response inhibitors in pancreatic cancer: progress and challenges.Frontiers in oncology · 2026Review
- The CIP2A-TOPBP1 axis facilitates mitotic DNA repair via MiDAS and MMEJ.Nature communications · 2025Article
- Homologous recombination deficiency among patients with germline or somatic non-BRCA1/2 homologous recombination repair gene variations.NPJ precision oncology · 2025Article
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- Homologous recombination deficiency (HRD) testing landscape: clinical applications and technical validation for routine diagnostics.Biomarker research · 2025Review
- Homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional immunofluorescence.Cell reports. Medicine · 2025Article
- Review
- Comprehensive Pan-Cancer Analysis Identifies IGFL1 as an Oncogenic Biomarker and Immunotherapeutic Target with Experimental Validation in Bladder Cancer.International journal of general medicine · 2025Article
- Analytical validation of a homologous recombination deficiency signature (HRDsig) in pan-tumor tissue samples.PloS one · 2025Article
- Integrated genomic and clinical modeling for prognostic assessment of radiotherapy response in rectal neoplasms.Open life sciences · 2025Article
- Prediction of homologous recombination deficiency from routine histology with attention-based multiple instance learning in nine different tumor types.BMC biology · 2024Article
- Is the Homologous Recombination Repair Mutation Defined by a 15-Gene Panel Associated with the Prognosis of Epithelial Ovarian Cancer?Molecular diagnosis & therapy · 2024Article
- Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
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Authors and funding
11 authors at 8 institutions in 7 countries.
Funding
Abstract
purposeTo study associations across tumor types between genome-wide loss of heterozygosity (gLOH) and alterations in homologous recombination repair (HRR)-associated genes beyond BRCA1 and BRCA2. EXPERIMENTAL
designGenomic profiling using a targeted next-generation sequencing assay examining 324-465 genes (FoundationOne, FoundationOne Heme, and FoundationOne CDx; Foundation Medicine, Inc.) was performed in a cohort of 160,790 samples across different tumor types. Zygosity predictions and gLOH status were calculated and linked with alterations in 18 HRR-associated genes (BRCA1, BRCA2, PALB2, BARD1, ATR, ATRX, ATM, BAP1, RAD51B, RAD51C, RAD51D, BRIP1, NBN, CHEK1, CHEK2, FANCA, FANCC, MRE11) and other genomic features, using Fisher's exact test and Mann-Whitney U tests.
resultsWe identified a strong correlation between elevated gLOH and biallelic alterations in a core set of HRR-associated genes beyond BRCA1 and BRCA2, such as BARD1, PALB2, FANCC, RAD51C, and RAD51D (particularly in breast, ovarian, pancreatic, and prostate cancer). Monoallelic/heterozygous alterations in HRR-associated genes were not associated with elevated gLOH. gLOH was also independently associated with TP53 loss. Co-occurrence of TP53 loss and alterations in HRR-associated genes, and combined loss of TP53-PTEN or TP53-RB1, was associated with a higher gLOH than each of the events separately.
conclusionsBiallelic alterations in core HRR-associated genes are frequent, strongly associated with elevated gLOH, and enriched in breast, ovarian, pancreatic, and prostate cancer. This analysis could inform the design of the next generation of clinical trials examining DNA repair-targeting agents, including PARP inhibitors.
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