波兰急性髓性白血病患者的种系突变

IF 2 4区 医学 Q3 ONCOLOGY Hereditary Cancer in Clinical Practice Pub Date : 2021-10-12 DOI:10.1186/s13053-021-00200-2
Aneta Bąk, Katarzyna Skonieczka, Anna Jaśkowiec, Anna Junkiert-Czarnecka, Marta Heise, Maria Pilarska-Deltow, Stanisław Potoczek, Maria Czyżewska, Olga Haus
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引用次数: 2

摘要

背景:一小部分但重要的AML患者(4- 10%)有种系突变。它们可以在更早的年龄导致AML的发展,赋予更高的复发风险或易患继发性白血病,包括治疗相关白血病。如果患者是造血干细胞移植(HSCT)的候选者,分析患者及其家庭的种系突变对于选择合适的家庭供体也至关重要。方法:103例无关联的连续新发AML患者入组研究。对照组由103名普通人群组成。我们对骨髓细胞和口腔拭子的六个基因CEBPA、DDX41、ETV6、TERT、GATA2和IDH2进行了NGS测序,以检测种系致病突变。结果:在调查组中,6个基因共检测到49个变异。其中体细胞26只,种系23只。在所有六个测试基因中均检测到种系变异。在7例AML患者中检测到8种致病种系突变,涉及3个基因:CEBPA、ETV6和IDH2。一名患者有两个致病的生发突变,一个在ETV6基因,一个在CEBPA基因。我们在CEBPA基因中发现了一种新的致病种系突变。各致病种系突变发生频率在试验组(7.77%)与对照组(0.97%)之间的差异有统计学意义(p = 0.046)。在试验组中,有致病性种系突变的患者诊断AML时的中位年龄比没有这种突变的患者低11岁(p = 0.028)。结论:我们发现,与对照组相比,AML患者中CEBPA、ETV6和IDH2种系突变的频率更高,这证实了这些突变在AML发展中的作用。我们还发现,具有致病性种系突变的AML患者发病的中位年龄明显低于没有这些突变的患者。
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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 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.

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来源期刊
CiteScore
3.10
自引率
5.90%
发文量
38
审稿时长
>12 weeks
期刊介绍: Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.
期刊最新文献
BRCA2 germline mutation carrier with five malignancies: a case report. A genome-wide association study in Swedish colorectal cancer patients with gastric- and prostate cancer in relatives. Breast cancer and ATM mutations: treatment implications. Meeting abstracts from the Annual Conference "Clinical Genetics of Cancer 2023". Validation of a guidelines-based digital tool to assess the need for germline cancer genetic testing.
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