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Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243048/ https://www.ncbi.nlm.nih.gov/pubmed/37277882 http://dx.doi.org/10.1186/s13104-023-06365-4 |
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author | Gunawardena, Kawmadi Sirisena, Nirmala D. Anandagoda, Gayani Neththikumara, Nilaksha Dissanayake, Vajira H.W. |
author_facet | Gunawardena, Kawmadi Sirisena, Nirmala D. Anandagoda, Gayani Neththikumara, Nilaksha Dissanayake, Vajira H.W. |
author_sort | Gunawardena, Kawmadi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10243048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-102430482023-06-07 Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer Gunawardena, Kawmadi Sirisena, Nirmala D. Anandagoda, Gayani Neththikumara, Nilaksha Dissanayake, Vajira H.W. BMC Res Notes Research Note 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. BioMed Central 2023-06-05 /pmc/articles/PMC10243048/ /pubmed/37277882 http://dx.doi.org/10.1186/s13104-023-06365-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Note Gunawardena, Kawmadi Sirisena, Nirmala D. Anandagoda, Gayani Neththikumara, Nilaksha Dissanayake, Vajira H.W. 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 |
title_full | Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer |
title_fullStr | Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer |
title_full_unstemmed | Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer |
title_short | Germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of Sri Lankan patients with hereditary breast cancer |
title_sort | germline variants of uncertain significance, their frequency, and clinico-pathological features in a cohort of sri lankan patients with hereditary breast cancer |
topic | Research Note |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243048/ https://www.ncbi.nlm.nih.gov/pubmed/37277882 http://dx.doi.org/10.1186/s13104-023-06365-4 |
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