Molecular analysis of pediatric myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML) by next generation sequencer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461611
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gunma Institute of Public Health and Environmental Sciences
• Principal Investigator: SOTOMATSU Manabu 群馬県衛生環境研究所, 研究企画係, 研究員 (70251113)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Yasuhide 群馬県衛生環境研究所, 研究企画係, 研究員 (30238133) ; 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

We analysed CSF3R exons 14 and 17, and calreticulin (CALR) exon 9, in pediatric AML(521 cases), JMML(40), MDS(20) and essential thrombocythemia (ET;21). CSF3R mutations were found in 10 (1.2%) of 521 patients with AML; 2 in exon 14 and 8 in exon 17. All of the patients with the mutations in CSF3R exon 17 had chromosomal translocations. No CSF3R mutations were found in cases of MDS, JMML or ET. CALR mutation was found in one ET patient. We examined 41 transient abnormal myelopoiesis (TAM), 49 DS-AMKL and 19 non-DS-AMKL samples by whole-exome sequencing. TAM appeared to be caused by a single GATA1 mutation and constitutive trisomy 21. Subsequent AMKL evolves through the acquisition of additional mutations, including cohesin components and other epigenetic regulators. We identified CBFA2T3-GLIS2, NUP98-JARID1A, and RBM15-MKL1, in 12, 4, and 2 patients out of 44 pediatric non-DS-AMKL patients. CBFA2T3-GLIS2 is considered to be a significant poor prognostic factor in non-DS-AMKL patients.

Free Research Field

小児血液・腫瘍学、分子細胞遺伝学