Mutational Landscape for Indian Hereditary Breast and Ovarian Cancer Cohort Suggests Need for Identifying Population Specific Genes and Biomarkers for Screening.

Autor:	Kadri MSN; Gujarat Biotechnology Research Centre, Department of Science and Technology, Government of Gujarat, Gandhinagar, India., Patel KM; Gujarat Biotechnology Research Centre, Department of Science and Technology, Government of Gujarat, Gandhinagar, India., Bhargava PA; Gujarat Biotechnology Research Centre, Department of Science and Technology, Government of Gujarat, Gandhinagar, India., Shah FD; Gujarat Cancer Research Institute, Civil Hospital, Ahmedabad, India., Badgujar NV; Gujarat Cancer Research Institute, Civil Hospital, Ahmedabad, India., Tarapara BV; Gujarat Cancer Research Institute, Civil Hospital, Ahmedabad, India., Patel PS; Gujarat Cancer Research Institute, Civil Hospital, Ahmedabad, India., Shaikh MI; Gujarat Biotechnology Research Centre, Department of Science and Technology, Government of Gujarat, Gandhinagar, India., Shah K; Clinical Genetics, ONE-Centre for Rheumatology and Genetics, Vadodara, India., Patel A; Gujarat Cancer Research Institute, Civil Hospital, Ahmedabad, India., Pandya S; Gujarat Cancer Research Institute, Civil Hospital, Ahmedabad, India., Vora H; Gujarat Cancer Research Institute, Civil Hospital, Ahmedabad, India., Joshi CG; Gujarat Biotechnology Research Centre, Department of Science and Technology, Government of Gujarat, Gandhinagar, India., Joshi MN; Gujarat Biotechnology Research Centre, Department of Science and Technology, Government of Gujarat, Gandhinagar, India.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2021 Jan 21; Vol. 10, pp. 568786. Date of Electronic Publication: 2021 Jan 21 (Print Publication: 2020).
DOI:	10.3389/fonc.2020.568786
Abstrakt:	Background: Breast and ovarian cancers are the most prevalent cancers and one of the leading causes of death in Indian women. The healthcare burden of breast and ovarian cancers and the rise in mortality rate are worrying and stress the need for early detection and treatment. Methods: We performed amplicon sequencing of 144 cases who had breast/ovarian cancer disease (total 137 cases are patients and seven are tested for BRCA1/2 carrier) Using our custom designed gene panel consisting of 14 genes, that are associated with high to moderate risk of breast and ovarian cancers. Variants were called using Torrent Variant Caller and were annotated using ThermoFisher's Ion Reporter software. Classification of variants and their clinical significance were identified by searching the variants against ClinVar database. Results: From a total of 144 cases, we were able to detect 42 pathogenic mutations in [40/144] cases. Majority of pathogenic mutations (30/41) were detected in BRCA1 gene, while (7/41) pathogenic mutations were detected in BRCA2 gene, whereas, (2/41) pathogenic mutations were detected in TP53 gene and BRIP1, PALB2, and ATM genes respectively. So, BRCA genes contributed 88.09% of pathogenic mutations, whereas non-BRCA genes contributed 11.91% of pathogenic mutations. We were also able to detect 25 VUS which were predicted to be damaging by in silico prediction tools. Conclusion: Early detection of cancers in the Indian population can be done by genetic screening using customized multi-gene panels. Indications of our findings show that in the Indian population, apart from the common BRCA genes, there are other genes that are also responsible for the disease. High frequency mutations detected in the study and variants of uncertain significance predicted to be damaging by in silico pathogenicity prediction tools can be potential biomarkers of hereditary breast and ovarian cancer in Indian HBOC patients. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Kadri, Patel, Bhargava, Shah, Badgujar, Tarapara, Patel, Shaikh, Shah, Patel, Pandya, Vora, Joshi and Joshi.)
Databáze:	MEDLINE
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