Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer.
| Title: | Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer. |
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| Authors: | Gunawardena K; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.; Sirisena ND; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka. nirmala@anat.cmb.ac.lk.; Anandagoda G; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.; Neththikumara N; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.; Dissanayake VHW; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka. |
| Source: | BMC research notes [BMC Res Notes] 2023 Jun 05; Vol. 16 (1), pp. 95. Date of Electronic Publication: 2023 Jun 05. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Biomed Central Country of Publication: England NLM ID: 101462768 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-0500 (Electronic) Linking ISSN: 17560500 NLM ISO Abbreviation: BMC Res Notes Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Biomed Central, 2008. |
| MeSH Terms: | Breast Neoplasms*/pathology; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Sri Lanka/epidemiology ; Germ Cells/pathology ; Humans ; Middle Aged ; Female ; Genetic Predisposition to Disease ; Retrospective Studies ; Germ-Line Mutation |
| Abstract: | Background: Next-Generation Sequencing (NGS)-based testing in cancer patients has led to increased detection of variants of uncertain significance (VUS). VUS are genetic variants whose impact on protein function is unknown. VUS pose a challenge to clinicians and patients due to uncertainty regarding their cancer predisposition risk. Paucity of data exists on the pattern of VUS in under-represented populations. This study describes the frequency of germline VUS and clinico-pathological features in Sri Lankan hereditary breast cancer patients.; Methods: Data of 72 hereditary breast cancer patients who underwent NGS-based testing between January 2015 and December 2021 were maintained prospectively in a database and analyzed retrospectively. Data were subjected to bioinformatics analysis and variants were classified according to international guidelines.; Results: Germline variants were detected in 33/72(45.8%) patients, comprising 16(48.5%) pathogenic/likely pathogenic variants and 17(51.5%) VUS. Distribution of VUS in breast cancer predisposing genes were :APC:1(5.8%), ATM:2(11.7%), BRCA1:1(5.8%), BRCA2:5(29.4%), BRIP1:1(5.8%), CDKN2A:1(5.8%), CHEK2:2(11.7%), FANC1:1(5.8%), MET:1(5.8%), STK11:1(5.8%), NF2:1(5.8%). Mean age at cancer diagnosis in patients with VUS was 51.2 years. Most common tumour histopathology was ductal carcinoma 11(78.6%). 50% of tumours in patients having VUS in BRCA1/2 genes were hormone receptor negative. 73.3% patients had family history of breast cancer.; Conclusions: A significant portion of patients had a germline VUS. Highest frequency was in BRCA2 gene. Majority had family history of breast cancer. This highlights the need to undertake functional genomic studies to determine the biological effects of VUS and identify potentially clinically actionable variants that would be useful for decision-making and patient management.; (© 2023. The Author(s).) |
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| Contributed Indexing: | Keywords: Breast cancer; Germline variants; Hereditary cancer; VUS; cancer phenotype |
| Substance Nomenclature: | 0 (BRCA1 protein, human); 0 (BRCA1 Protein); 0 (BRCA2 protein, human); 0 (BRCA2 Protein) |
| SCR Disease Name: | Breast Cancer, Familial |
| Entry Date(s): | Date Created: 20230605 Date Completed: 20230607 Latest Revision: 20230608 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10243048 |
| DOI: | 10.1186/s13104-023-06365-4 |
| PMID: | 37277882 |
| Database: | MEDLINE |
Journal Article