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Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme
Breast and ovarian cancers are among the most common malignancies in the female population, with approximately 5–10% of cases being hereditary. BRCA1 and BRCA2 with other homologous recombination genes are the most tested genes in hereditary breast and ovarian cancer (HBOC) patients. As next-generat...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510890/ https://www.ncbi.nlm.nih.gov/pubmed/36171877 http://dx.doi.org/10.3389/fgene.2022.941375 |
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author | Doraczynska-Kowalik, Anna Michalowska, Dagmara Matkowski, Rafal Czykalko, Ewelina Blomka, Dorota Semeniuk, Mariola Abrahamowska, Mariola Janus-Szymanska, Gabriela Mlynarczykowska, Paulina Szynglarewicz, Bartlomiej Pawlak, Ireneusz Maciejczyk, Adam Laczmanska, Izabela |
author_facet | Doraczynska-Kowalik, Anna Michalowska, Dagmara Matkowski, Rafal Czykalko, Ewelina Blomka, Dorota Semeniuk, Mariola Abrahamowska, Mariola Janus-Szymanska, Gabriela Mlynarczykowska, Paulina Szynglarewicz, Bartlomiej Pawlak, Ireneusz Maciejczyk, Adam Laczmanska, Izabela |
author_sort | Doraczynska-Kowalik, Anna |
collection | PubMed |
description | Breast and ovarian cancers are among the most common malignancies in the female population, with approximately 5–10% of cases being hereditary. BRCA1 and BRCA2 with other homologous recombination genes are the most tested genes in hereditary breast and ovarian cancer (HBOC) patients. As next-generation sequencing (NGS) has become a standard and popular technique, such as for HBOC, it has greatly simplified and accelerated molecular diagnosis of cancer. The study group included 3,458 HBOC patients or their relatives from Lower Silesia (Poland) (a voivodeship located in south-west Poland inhabited by 2.9 million people). All patients were tested according to the recommendations from the National Cancer Control Programme of the Ministry of Health for the years 2018–21. We tested 3,400 patients for recurrent pathogenic variants for the Polish population: five BRCA1 founder variants (c.5266dup, c.181T>G, c.4035del, c.3700_3704del, and c.68_69del), two PALB2 variants (c.509_510del, c.172_175del) and three CHEK2 variants [c.1100del, c.444+1G>A, g.27417113-27422508del (del5395)]. Next 260 patients from the study group were chosen for the BRCA1/2 NGS panel, and additionally selected marker pathogenic variants were tested using Sanger sequencing and MLPA methods in 45 and 13 individuals, respectively. The analysis of BRCA1/2 in the 3,458 patients with HBOC or their relatives revealed 144 carriers of 37 different pathogenic variants (22 in BRCA1 and 15 in BRCA2). Among all detected variants, 71.53% constituted founder pathogenic BRCA1 variants. Our study has revealed that for the Lower Silesian population, the first-line BRCA1/2 molecular test may be limited to only three variants in BRCA1—c.5266dup, c.181T>G, and c.4035del—but the aim should be to provide a full screening test of HBOC critical genes. The key and still growing role of molecular diagnostics of neoplasms, which includes HBOC, is undeniable. Therefore, it is necessary to provide complete and optimal therapeutic and prophylactic algorithms in line with current medical knowledge. |
format | Online Article Text |
id | pubmed-9510890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95108902022-09-27 Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme Doraczynska-Kowalik, Anna Michalowska, Dagmara Matkowski, Rafal Czykalko, Ewelina Blomka, Dorota Semeniuk, Mariola Abrahamowska, Mariola Janus-Szymanska, Gabriela Mlynarczykowska, Paulina Szynglarewicz, Bartlomiej Pawlak, Ireneusz Maciejczyk, Adam Laczmanska, Izabela Front Genet Genetics Breast and ovarian cancers are among the most common malignancies in the female population, with approximately 5–10% of cases being hereditary. BRCA1 and BRCA2 with other homologous recombination genes are the most tested genes in hereditary breast and ovarian cancer (HBOC) patients. As next-generation sequencing (NGS) has become a standard and popular technique, such as for HBOC, it has greatly simplified and accelerated molecular diagnosis of cancer. The study group included 3,458 HBOC patients or their relatives from Lower Silesia (Poland) (a voivodeship located in south-west Poland inhabited by 2.9 million people). All patients were tested according to the recommendations from the National Cancer Control Programme of the Ministry of Health for the years 2018–21. We tested 3,400 patients for recurrent pathogenic variants for the Polish population: five BRCA1 founder variants (c.5266dup, c.181T>G, c.4035del, c.3700_3704del, and c.68_69del), two PALB2 variants (c.509_510del, c.172_175del) and three CHEK2 variants [c.1100del, c.444+1G>A, g.27417113-27422508del (del5395)]. Next 260 patients from the study group were chosen for the BRCA1/2 NGS panel, and additionally selected marker pathogenic variants were tested using Sanger sequencing and MLPA methods in 45 and 13 individuals, respectively. The analysis of BRCA1/2 in the 3,458 patients with HBOC or their relatives revealed 144 carriers of 37 different pathogenic variants (22 in BRCA1 and 15 in BRCA2). Among all detected variants, 71.53% constituted founder pathogenic BRCA1 variants. Our study has revealed that for the Lower Silesian population, the first-line BRCA1/2 molecular test may be limited to only three variants in BRCA1—c.5266dup, c.181T>G, and c.4035del—but the aim should be to provide a full screening test of HBOC critical genes. The key and still growing role of molecular diagnostics of neoplasms, which includes HBOC, is undeniable. Therefore, it is necessary to provide complete and optimal therapeutic and prophylactic algorithms in line with current medical knowledge. Frontiers Media S.A. 2022-09-12 /pmc/articles/PMC9510890/ /pubmed/36171877 http://dx.doi.org/10.3389/fgene.2022.941375 Text en Copyright © 2022 Doraczynska-Kowalik, Michalowska, Matkowski, Czykalko, Blomka, Semeniuk, Abrahamowska, Janus-Szymanska, Mlynarczykowska, Szynglarewicz, Pawlak, Maciejczyk and Laczmanska. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Doraczynska-Kowalik, Anna Michalowska, Dagmara Matkowski, Rafal Czykalko, Ewelina Blomka, Dorota Semeniuk, Mariola Abrahamowska, Mariola Janus-Szymanska, Gabriela Mlynarczykowska, Paulina Szynglarewicz, Bartlomiej Pawlak, Ireneusz Maciejczyk, Adam Laczmanska, Izabela Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme |
title | Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme |
title_full | Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme |
title_fullStr | Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme |
title_full_unstemmed | Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme |
title_short | Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme |
title_sort | detection of brca1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. analysis of 3,458 cases from lower silesia (poland) according to the diagnostic algorithm of the national cancer control programme |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510890/ https://www.ncbi.nlm.nih.gov/pubmed/36171877 http://dx.doi.org/10.3389/fgene.2022.941375 |
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