Longitudinal whole-genome sequencing reveals the evolution of MPAL
| Autor: | Xuehong Zhang, Jingkai Zhang, Yulong Li, Yuwei Liao, Jichao Tian, Mengying Tong, Dekang Lv, Wanting Bai, Ruimei Liu, Dongcen Ge, Yichen Wang, Jinsong Yan, Yu Zhang, Zhijie Kang, Chao Huang, Quentin Liu, Zhiguang Li, Peiying Li, Yanyan Shao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty DNA Copy Number Variations medicine.medical_treatment DNA Mutational Analysis Disease Biology Clonal Evolution 03 medical and health sciences 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols Genetics medicine Humans Philadelphia Chromosome Longitudinal Studies Indel Molecular Biology Whole genome sequencing Chemotherapy Acute leukemia Philadelphia Chromosome Positive Whole Genome Sequencing medicine.disease Primary tumor Leukemia Biphenotypic Acute medicine.anatomical_structure 030220 oncology & carcinogenesis Disease Progression Bone marrow Neoplasm Recurrence Local |
| Zdroj: | Cancer Genetics. 240:59-65 |
| ISSN: | 2210-7762 |
| DOI: | 10.1016/j.cancergen.2019.11.007 |
| Popis: | Purpose Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia and its progressive genomic basis over time remains unclear. We aimed to investigate the longitudinal genomic evolution of MPAL from diagnosis to relapse. Methods We performed whole genome sequencing (WGS) on bone marrow (BM) samples obtained at the four stages of this disease in a male patient with Philadelphia chromosome positive (Ph+) MPAL, including primary, complete cytogenetic remission (CCR), complete molecular remission (CMR), and relapse stage during the 3 year follow-up period. Results 156 single-nucleotide variants (SNVs) and indels were detected, which exhibited distinctive evolutionary behaviors. Seventeen mutations disappeared quickly upon DCTER treatment and never came back. Seven mutations, although disappeared initially, reoccurred with the withdrawal of TKI treatment. Notably, ten mutations emerged in spite of the active DCTER chemotherapy. Moreover, copy number loss played critical roles in monitoring MPAL progression, displaying 7, 0, 0, and 383 losses at the stages of primary, CCR, CMR, and relapse respectively. Conclusion This longitudinal genomic investigation of the Ph+ MPAL patient established one MPAL evolution model in which the primary tumor acquired additional variations leading to tumor relapse. Moreover, the event of copy number loss remained a valuable hallmark in the progression of MPAL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect