Clonal evolution analyses between relapse and diagnosis samples in pediatric acute myeloid leukemia by next generation sequencer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670482
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Gunma Institute of Public Health and Environmental Sciences
• Principal Investigator: HAYASHI Yasuhide 群馬県衛生環境研究所, 研究企画係, 研究員 (30238133)
• Co-Investigator(Kenkyū-buntansha): OHKI Kentarou 国立成育医療研究センター, 小児血液・腫瘍研究部, 室長 (50400966) ; PARK Myoung-ja 群馬県衛生環境研究所, 研究企画係, 研究員 (50450375)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 遺伝子 / ゲノム / マイクロアレイ / 癌 / 臨床

Outline of Final Research Achievements

Whole-exome resequencing of 19 cases with acute myeloid leukemia (AML) at diagnosis and 10 cases both at diagnosis and relapse was performed with a mean coverage of approximately x100. Several genes including BCOR/BCORL1 and RAD21 were newly identified. Furthermore, we examined mutations of these genes in pediatric 192 AML patients by gene targeting. In total, 32 mutations were identified in 31 of these specimens. The mutually exclusive pattern of the mutations in these BCOR/BCORL1 and cohesin components genes was identified, however, no associations of these genes with the prognosis were found. Transcriptome analysis of AML cases with MEL1 high expression identified novel chimeric fusions, and clonal evolutions were found. Our results indicated that a subset of subclone emerged at relapse, suggesting heterogeneity in AML. Extensive methylation analysis is going to be done.

Free Research Field

小児血液・腫瘍学、分子細胞遺伝学