Germline mutations among Polish patients with acute myeloid leukemia
Abstract 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 mut...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Hereditary Cancer in Clinical Practice |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13053-021-00200-2 |
| _version_ | 1819148522817060864 |
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| author | Aneta Bąk Katarzyna Skonieczka Anna Jaśkowiec Anna Junkiert-Czarnecka Marta Heise Maria Pilarska-Deltow Stanisław Potoczek Maria Czyżewska Olga Haus |
| author_facet | Aneta Bąk Katarzyna Skonieczka Anna Jaśkowiec Anna Junkiert-Czarnecka Marta Heise Maria Pilarska-Deltow Stanisław Potoczek Maria Czyżewska Olga Haus |
| author_sort | Aneta Bąk |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-22T13:47:03Z |
| format | Article |
| id | doaj.art-47c78243390c4d95a4e75a4a4b5b9c76 |
| institution | Directory Open Access Journal |
| issn | 1897-4287 |
| language | English |
| last_indexed | 2024-12-22T13:47:03Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditary Cancer in Clinical Practice |
| spelling | doaj.art-47c78243390c4d95a4e75a4a4b5b9c762022-12-21T18:23:45ZengBMCHereditary Cancer in Clinical Practice1897-42872021-10-0119111110.1186/s13053-021-00200-2Germline mutations among Polish patients with acute myeloid leukemiaAneta Bąk0Katarzyna Skonieczka1Anna Jaśkowiec2Anna Junkiert-Czarnecka3Marta Heise4Maria Pilarska-Deltow5Stanisław Potoczek6Maria Czyżewska7Olga Haus8Department of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus UniversityDepartment of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus UniversityDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical UniversityDepartment of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus UniversityDepartment of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus UniversityDepartment of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus UniversityDepartment of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical UniversityDepartment of Hematology, Municipal HospitalDepartment of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus UniversityAbstract 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.https://doi.org/10.1186/s13053-021-00200-2Acute myeloid leukemiaAMLgermline mutationsCEBPADDX41ETV6 |
| spellingShingle | Aneta Bąk Katarzyna Skonieczka Anna Jaśkowiec Anna Junkiert-Czarnecka Marta Heise Maria Pilarska-Deltow Stanisław Potoczek Maria Czyżewska Olga Haus Germline mutations among Polish patients with acute myeloid leukemia Hereditary Cancer in Clinical Practice Acute myeloid leukemia AML germline mutations CEBPA DDX41 ETV6 |
| 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 | Acute myeloid leukemia AML germline mutations CEBPA DDX41 ETV6 |
| url | https://doi.org/10.1186/s13053-021-00200-2 |
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