Mutational Landscape for Indian Hereditary Breast and Ovarian Cancer Cohort Suggests Need for Identifying Population Specific Genes and Biomarkers for Screening
| Autor: | Franky D. Shah, Shashank Pandya, Poonam Bhargava, Chaitanya G. Joshi, Apurva Patel, Nutan V. Badgujar, Bhoomi V. Tarapara, Komal Patel, Madhvi Joshi, Mohammed Inayatullah Shaikh, Prabhudas S. Patel, Krati Shah, Mohammed Shaad N Kadri, Hemangini H. Vora |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research endocrine system diseases In silico PALB2 Disease Biology hereditary breast and ovarian cancer lcsh:RC254-282 customized multi-gene panel genetic testing 03 medical and health sciences 0302 clinical medicine medicine Clinical significance BRCA1 and BRCA2 Gene Original Research Genetic testing next generation sequencing Genetics amplicon sequencing medicine.diagnostic_test BRIP1 lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Ovarian cancer non-BRCA genes |
| Zdroj: | Frontiers in Oncology, Vol 10 (2021) Frontiers in Oncology |
| ISSN: | 2234-943X |
| Popis: | BackgroundBreast 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.MethodsWe 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.ResultsFrom 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.ConclusionEarly 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. |
| Databáze: | OpenAIRE |
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