Analysis of somatic mutation for adult T-cell leukemia using a next-generation sequencing

• Project/Area Number: 24591392
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: HISHIZAWA Masakatsu 京都大学, 医学(系)研究科(研究院), 助教 (90444455)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 成人T細胞白血病 / NF-kB / ＡＴＬ / ＮＦ－kＢ / 血液内科

Outline of Final Research Achievements

To elucidate the molecular mechanism of NF-kB activation for adult T-cell leukemia (ATL), we examined somatic mutation of ATL cells using next-generation DNA sequencing. Among 27 ATL patients evaluated, there was no non-synonymous mutation for A20, BCL11B, CARD11, MYD88, or NIK. However, two patients with ATL had CARD11 mutation at coiled-coil domain (M360V, D401Y). These mutations showed NF-kB activation by luciferase reporter assay. CARD11 could contribute a constitutive activation of NF-kB for ATL.