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Germline mutations among Polish patients with acute myeloid leukemia
BACKGROUND: A small but important proportion of patients (4–10 %) with AML have germline mutations. They can cause the development of AML at an earlier age, confer a higher risk of relapse or predispose to secondary leukemias, including therapy-related leukemias. The analysis of germline mutations i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507332/ https://www.ncbi.nlm.nih.gov/pubmed/34641967 http://dx.doi.org/10.1186/s13053-021-00200-2 |
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author | Bąk, Aneta Skonieczka, Katarzyna Jaśkowiec, Anna Junkiert-Czarnecka, Anna Heise, Marta Pilarska-Deltow, Maria Potoczek, Stanisław Czyżewska, Maria Haus, Olga |
author_facet | Bąk, Aneta Skonieczka, Katarzyna Jaśkowiec, Anna Junkiert-Czarnecka, Anna Heise, Marta Pilarska-Deltow, Maria Potoczek, Stanisław Czyżewska, Maria Haus, Olga |
author_sort | Bąk, Aneta |
collection | PubMed |
description | BACKGROUND: A small but important proportion of patients (4–10 %) with AML have germline mutations. They can cause the development of AML at an earlier age, confer a higher risk of relapse or predispose to secondary leukemias, including therapy-related leukemias. The analysis of germline mutations in a patient and his/her family is also critical for the selection of suitable family donors if the patient is a candidate for hematopoietic stem cell transplantation (HSCT). METHODS: 103 unrelated consecutive patients with de novo AML were enrolled in the study. Control group consisted of 103 persons from the general population. We performed NGS sequencing of bone marrow cells and buccal swabs DNA of six genes: CEBPA, DDX41, ETV6, TERT, GATA2, and IDH2 to detect germline pathogenic mutations. RESULTS: In the investigated group, 49 variants were detected in six genes. 26 of them were somatic and 23 germline. Germline variants were detected in all six tested genes. Eight pathogenic germline mutations were detected in 7 AML patients, in three genes: CEBPA, ETV6, and IDH2. One patient had two pathogenic germinal mutations, one in ETV6 and one in CEBPA gene. We identified one novel pathogenic germline mutation in CEBPA gene. The difference in frequency of all pathogenic germline mutations between the tested (7.77 %) and control groups (0.97 %) was statistically significant (p = 0.046). In the tested group, the median age at AML diagnosis was 11 years lower in patients with pathogenic germline mutations than in patients without them (p = 0.028). CONCLUSIONS: We showed higher frequency of CEBPA, ETV6, and IDH2 germline mutations in AML patients than in control group, which confirms the role of these mutations in the development of AML. We also showed that the median age at the onset of AML in patients with pathogenic germline mutations is significantly lower than in patients without them. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13053-021-00200-2. |
format | Online Article Text |
id | pubmed-8507332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-85073322021-10-20 Germline mutations among Polish patients with acute myeloid leukemia Bąk, Aneta Skonieczka, Katarzyna Jaśkowiec, Anna Junkiert-Czarnecka, Anna Heise, Marta Pilarska-Deltow, Maria Potoczek, Stanisław Czyżewska, Maria Haus, Olga Hered Cancer Clin Pract Research BACKGROUND: A small but important proportion of patients (4–10 %) with AML have germline mutations. They can cause the development of AML at an earlier age, confer a higher risk of relapse or predispose to secondary leukemias, including therapy-related leukemias. The analysis of germline mutations in a patient and his/her family is also critical for the selection of suitable family donors if the patient is a candidate for hematopoietic stem cell transplantation (HSCT). METHODS: 103 unrelated consecutive patients with de novo AML were enrolled in the study. Control group consisted of 103 persons from the general population. We performed NGS sequencing of bone marrow cells and buccal swabs DNA of six genes: CEBPA, DDX41, ETV6, TERT, GATA2, and IDH2 to detect germline pathogenic mutations. RESULTS: In the investigated group, 49 variants were detected in six genes. 26 of them were somatic and 23 germline. Germline variants were detected in all six tested genes. Eight pathogenic germline mutations were detected in 7 AML patients, in three genes: CEBPA, ETV6, and IDH2. One patient had two pathogenic germinal mutations, one in ETV6 and one in CEBPA gene. We identified one novel pathogenic germline mutation in CEBPA gene. The difference in frequency of all pathogenic germline mutations between the tested (7.77 %) and control groups (0.97 %) was statistically significant (p = 0.046). In the tested group, the median age at AML diagnosis was 11 years lower in patients with pathogenic germline mutations than in patients without them (p = 0.028). CONCLUSIONS: We showed higher frequency of CEBPA, ETV6, and IDH2 germline mutations in AML patients than in control group, which confirms the role of these mutations in the development of AML. We also showed that the median age at the onset of AML in patients with pathogenic germline mutations is significantly lower than in patients without them. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13053-021-00200-2. BioMed Central 2021-10-12 /pmc/articles/PMC8507332/ /pubmed/34641967 http://dx.doi.org/10.1186/s13053-021-00200-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 Bąk, Aneta Skonieczka, Katarzyna Jaśkowiec, Anna Junkiert-Czarnecka, Anna Heise, Marta Pilarska-Deltow, Maria Potoczek, Stanisław Czyżewska, Maria Haus, Olga Germline mutations among Polish patients with acute myeloid leukemia |
title | Germline mutations among Polish patients with acute myeloid leukemia |
title_full | Germline mutations among Polish patients with acute myeloid leukemia |
title_fullStr | Germline mutations among Polish patients with acute myeloid leukemia |
title_full_unstemmed | Germline mutations among Polish patients with acute myeloid leukemia |
title_short | Germline mutations among Polish patients with acute myeloid leukemia |
title_sort | germline mutations among polish patients with acute myeloid leukemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507332/ https://www.ncbi.nlm.nih.gov/pubmed/34641967 http://dx.doi.org/10.1186/s13053-021-00200-2 |
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