한빛사논문
- 조회1,170
Abstract
T Kim1,2, M S Tyndel2,3, H J Kim4,5, J-S Ahn4,5, S H Choi4, H J Park4, Y-k Kim4,5, D-H Yang5, J-J Lee5, S-H Jung5, S Y Kim4,5, Y H Min6, J-W Cheong6, S K Sohn7, J H Moon7, M Choi8, M Lee8, Z Zhang1,2,9 and D(D H) Kim10
1Department of Computer Science, University of Toronto, Toronto, ON, Canada
2The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada
3The Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada
4Genome Research Center for Hematopoietic Disease, Chonnam National University, Hwasun, Korea
5Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
6Department of Internal Medicine, Yonsei University, Seoul, Korea
7Department of Hematology-Oncology, Kyungpook National University, Daegu, Korea
8Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
9Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
10Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
Correspondence: Dr HJ Kim or Dr Z Zhang, Genome Research Center for Hematopoietic Disease, College of Medicine, Chonnam National University, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun 519-763, Jeollanam-do, Republic of Korea or, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College St., Rm 608, Toronto, ON, Canada M5S 3E1.
Abstract
The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.
논문정보
- Research article
- 2017년 02월 (BRIC 등록일 2017-02-10)
- 국내(교신)+국외 연구진
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