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Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India

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Abstract

Background

The frequency of triple-negative breast cancer (TNBC) incidence varies among different populations suggesting the involvement of genetic components towards TNBC development. Previous studies have reported that BRCA1/2 germline mutations confer a lifetime risk of developing TNBC. However, there is hardly any information regarding the common pathogenic variants (PVs) in BRCA1/2 genes that contribute to TNBC in the Indian population. Hence, we screened for PVs in BRCA1/2 and their association with clinico-pathological features in TNBC patients.

Methods and results

The study recruited 59 TNBC patients without hereditary breast and ovarian cancer (HBOC) from South India. The entire BRCA1 and BRCA2 genes were sequenced for the 59 patients using the Illumina HiSeq X Ten sequencer. Among the 59 TNBC genomic DNA samples sequenced, BRCA mutations were identified in 8 patients (13.6%), BRCA1 mutations in 6 patients, and BRCA2 mutations in 2 patients. Among the 6 BRCA1 mutations, three were c.68_69delAG (185delAG) mutation. Remarkably, all the TNBC patients with BRCA mutations exhibited higher-grade tumors (grade 2 or 3). However, among all the BRCA mutation carriers, only one patient with a BRCA2 mutation (p.Glu1879Lys) developed metastasis.

Conclusion

Our data advocates that South Indian women with higher grade TNBC tumors and without HBOC could be considered for BRCA mutation screening, thereby enabling enhanced decision-making and preventive therapy.

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Acknowledgements

The authors express their deep gratitude to all the study participants who volunteered in the study and the medical staff of Dr. G.V.N Cancer Institute. The authors also thank SASTRA—Deemed University for infrastructural support. The authors also thank the support of MEDGENOME, Bangalore, India during sample sequencing.

Funding

This study was funded by the Department of Science and Technology, SERB—Government of India (YSS/2015/001692) and Oncoclub, Chennai.

Author information

Authors and Affiliations

  1. Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA – Deemed University, Thanjavur, 613 401, India

    Taruna Rajagopal & Nageswara Rao Dunna

  2. Department of Medical and Paediatric Oncology, Dr.G.V.N Cancer Institute, Singarathope, Trichy, 620 008, India

    Arun Seshachalam

  3. Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA – Deemed University, Thanjavur, 613 401, India

    Arunachalam Jothi

  4. Department of Hemato Oncology – Medical Oncology and Bone Marrow Transplantation, Meenakshi Mission Hospital & Research Centre, Madurai, 625 107, India

    Krishna Kumar Rathnam

  5. Dana Farber Cancer Institute, Boston, MA, 02215, USA

    Srikanth Talluri

  6. Veterans Administration Boston Healthcare System, West Roxbury, MA, 02132, USA

    Srikanth Talluri

  7. Department of Genetic Engineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur Campus, Chennai, Tamil Nadu, 603 203, India

    Sivaramakrishnan Venkatabalasubranian

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  1. Taruna Rajagopal
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Contributions

TR: data curation, formal analysis, investigation, methodology, writing—original draft, writing—review & editing. AS: methodology, resources, supervision. AJ: data analysis, validation, software. KKR: methodology, resources. ST: investigation, supervision, review & editing; SV: review & editing; NRD: conceptualization, funding acquisition, project administration, resources, investigation, validation, supervision, writing—review & editing.

Corresponding author

Correspondence to Nageswara Rao Dunna.

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The authors declare that they have no conflict of interest.

Ethical approval

Study proceeded with the approval of ethical committee Dr. G.V.N cancer Institute (GVNCI-IEC—ECR/436/INST/TN/2013).

Informed consent

Informed consent was obtained from all the individual participants included in the study.

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Rajagopal, T., Seshachalam, A., Jothi, A. et al. Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India. Mol Biol Rep 49, 3025–3032 (2022). https://doi.org/10.1007/s11033-022-07129-2

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