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

Abstract

Background Therapy-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. Methods A 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. Results The 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). Conclusion The 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.

Acute Myeloid Leukemia Post Cytotoxic Therapy in Breast Cancer Survivors—Over 23 Years of Single Center Analysis

“…Over the past two decades, with BC being the most frequently identified prior malignancy, our finding revealed that AML-pCT after BC accounted for 35% of all AML-pCT cases. This stands in contrast to other studies, in which BC had a lower frequency and lymphomas were more commonly observed [16][17][18]. The total incidence of AML-pCT in our report (9.4%) was comparable to that in others [19,20].…”

Multiple Primary Cancers With Hematologic Malignancies and Germline Predisposition: A Case Series

“…Germline variants in genes associated with inherited cancer susceptibility, such as BARD1, BRCA1, BRCA2, CHEK2, TP53, and the Fanconi anemia genes, are identified in approximately 16%-21% of patients diagnosed with T-MN [13][14][15]. In our previous study involving 53 T-MN patients in Korea, seven patients (13.2%) presented deleterious presumed/potential germline variants in cancer predisposition genes (CPGs), such as BRIP1, CEBPA, DDX41, FANCM, NBN, NF1, and RUNX1 [16]. Using whole-genome sequencing, Whitworth et al [10] detected pathogenic germline variants in CPGs in 67 (15.2%) out of 440 patients with MP cancers.…”

“…We report five patients with MP cancers and hematologic malignancies and describe their clinical characteristics, cytogenetic profiles, and germline and somatic variants. The five patients were identified during our previous study on T-MN at a single institution in Korea [ 16 ] and were selected for the present study based on T-MN diagnostic criteria. The patients were diagnosed as having two distinct cancers with more than a six-month gap, and their diagnoses adhered to both the SEER and IACR/IARC MP cancer criteria.…”

“…Using bone marrow (BM) aspirates of the five patients obtained after the diagnosis of the second cancer (hematologic malignancies), chromosome analysis, interphase FISH, and targeted next-generation sequencing was performed, as previously described [ 16 ]. The only difference from the previous study lay in the variant filtering strategy used: in the present study, only tier I and II variants were selected in somatic mutation analysis, according to the guidelines of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists [ 18 ].…”

“…Patient MP2 harbored a 17/17p deletion in their second cancer, MDS. Although monosomy 5 or 7, 5q or 7q deletion are commonly observed cytogenetic abnormalities in T-MN, 17/17p deletion is also observed in some T-MN cases [ 16 ]. Three patients (MP1, MP3, and MP5) whose second cancers were MPN harbored a JAK2 V617F somatic mutation.…”