Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea

被引：4

作者：

Yun, Jiwon ^{[1
,2
]}

Song, Hyojin ^{[3
]}

Kim, Sung-Min ^{[4
]}

Kim, Soonok ^{[5
]}

Kwon, Seok Ryun ^{[1
]}

Lee, Young Eun ^{[1
]}

Jeong, Dajeong ^{[1
]}

Park, Jae Hyeon ^{[1
]}

Kwon, Sunghoon ^{[6
,7
]}

Yun, Hongseok ^{[3
]}

Lee, Dong Soon ^{[1
,4
,8
]}

机构：

[1] Seoul Natl Univ Coll Med, Dept Lab Med, 101 Daehak Ro, Seoul 03080, South Korea

[2] Chung Ang Univ Hosp, Dept Lab Med, Seoul, South Korea

[3] Seoul Natl Univ Hosp, Dept Genom Med, 101 Daehak Ro, Seoul 03080, South Korea

[4] Seoul Natl Univ Coll Med, Canc Res Inst, Seoul, South Korea

[5] Seoul Natl Univ Hosp, Dept Lab Med, Seoul, South Korea

[6] Seoul Natl Univ, Dept Elect & Comp Engn, Seoul, South Korea

[7] Seoul Natl Univ, Biomax Inst, Seoul, South Korea

[8] Seoul Natl Univ Med Res Ctr, Genom Med Inst, Seoul, South Korea

来源：

HUMAN GENOMICS | 2023年 / 17卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Therapy-related myeloid neoplasm; Next-generation sequencing; Germline predisposition; Somatic mutation; JOINT-CONSENSUS-RECOMMENDATION; BONE-MARROW MICROENVIRONMENT; DNA-DAMAGE; CLONAL HEMATOPOIESIS; GERMLINE MUTATIONS; SEQUENCE VARIANTS; PPM1D MUTATIONS; STEM-CELLS; PREDISPOSITION; PROTEIN;

D O I：

10.1186/s40246-023-00458-8

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

BackgroundTherapy-related myeloid neoplasm (T-MN) rarely occurs among cancer survivors, and was characterized by poor prognosis. T-MN has germline predisposition in a considerable proportion. Here, clinical characteristics and germline/somatic variant profiles in T-MN patients were investigated, and the findings were compared with those of previous studies.MethodsA review of medical records, cytogenetic study, targeted sequencing by next-generation sequencing, and survival analysis were performed on 53 patients with T-MN at a single institution in Korea.ResultsThe patients were relatively younger compared to T-MN patients in other studies. Our T-MN patients showed a high frequency of complex karyotypes, -5/del(5q), and -7/del(7q), which was similar to the Japanese study group but higher than the Australian study group. The most common primary disease was non-Hodgkin lymphoma, followed by breast cancer. The detailed distributions of primary diseases were different across study groups. Seven patients (13.2%) harbored deleterious presumed/potential germline variants in cancer predisposition genes (CPG) such as BRIP1, CEBPA, DDX41, FANCM, NBN, NF1, and RUNX1. In the somatic variant profile, TP53 was the most frequently mutated gene, which was consistent with the previous studies about T-MN. However, the somatic variant frequency in our study group was lower than in other studies. Adverse factors for overall survival were male sex, older age, history of previous radiotherapy, previous longer cytotoxic therapy, and -5/del(5q).ConclusionThe findings of our study corroborate important information about T-MN patients. As well as a considerable predisposition to CPG, the clinical characteristics and somatic variant profile showed distinctive patterns. Germline variant testing should be recommended for T-MN patients. If the T-MN patients harbor pathogenic germline variants, the family members for stem cell donation should be screened for carrier status through germline variant testing to avoid donor-derived myeloid neoplasm. For the prediction of the prognosis in T-MN patients, sex, age, past treatment history, and cytogenetic findings can be considered.

引用

页数：19