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Updated: Aug 15, 2026
08:53
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
Uncovering Hereditary Risk: Germline Homologous Recombination Repair Variant Spectrum in a Large North Indian Cancer
Akhil Kapoor1, Srushti Uthale2, Anamika Chain2
1Medical Oncology, Mahamana Pandit Madanmohan Malaviya Cancer Centre & Homi Bhabha Cancer Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Varanasi, India.
JCO Global Oncology
|August 13, 2026
Summary
Homologous recombination repair (HRR) gene alterations are common in Indian cancer patients, with non-BRCA genes playing a significant role. Comprehensive HRR panel testing is crucial for identifying patients eligible for targeted therapies.
Area of Science:
- Genetics and Genomics
- Oncology
- Cancer Research
Background:
- Homologous recombination repair (HRR) pathway defects are key drivers of hereditary cancers.
- Limited population-specific prevalence data exists for India.
- Current testing often focuses solely on BRCA1/2, potentially missing other actionable HRR variants.
Purpose of the Study:
- To determine the prevalence of HRR gene alterations in an Indian cohort.
- To assess the contribution of non-BRCA HRR genes to hereditary cancers in India.
- To inform diagnostic and therapeutic strategies for Indian cancer patients.
Main Methods:
- Retrospective observational cohort study of 950 consecutive patients.
- Germline testing using a comprehensive next-generation sequencing HRR gene panel.
- Analysis of variants in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATM, CHEK2, BRIP1, BARD1, RAD50, NBN, MRE11, and FANCC.
Main Results:
- 38.3% of patients had variants in HRR genes; 28% had pathogenic/likely pathogenic (P/LP) variants.
- BRCA1 (68.4%) and BRCA2 (13.9%) were the most frequent P/LP variants.
- Non-BRCA HRR genes accounted for 17.6% of P/LP variants, with PALB2 being most common (5.2%).
Conclusions:
- A high prevalence of HRR gene alterations, including non-BRCA genes, was observed in this Indian cohort.
- Comprehensive HRR gene panel testing is recommended for Indian populations.
- Findings support targeted therapies like PARP inhibitors and platinum-based treatments.
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