Deletion of the 3p region in malignant mesothelioma cells derived from Japanese patients

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590715
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Hyogo Medical University
• Principal Investigator: HASHIMOTO-TAMAOKI Tomoko 兵庫医科大学, 医学部, 教授 (10172868)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Yoshie 兵庫医科大学, 医学部, 助教 (10566673) ; MORINAGA Tomonori 兵庫医科大学, 医学部, 非常勤講師 (10351818) ; KUBO Shuji 兵庫医科大学, 医学部, 准教授 (10441320)
• Co-Investigator(Renkei-kenkyūsha): EMI Mitsuru 兵庫医科大学, 医学部, 特別招聘教授 (90221118) ; SHIMA Hiroki 兵庫医科大学, 医学部, 名誉教授 (90104257)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 悪性中皮腫 / 3p領域 / BAP1遺伝子 / クロマチンリモデリング / 転写制御 / HDAC阻害剤 / ゲノム多型 / 易罹患性

Outline of Final Research Achievements

The BAP1 gene, one of the histone modifiers, on 3p21.1 is frequently deleted or mutated in the malignant mesothelioma (MM) cell lines established from sporadic Japanese cases. We established the MLPA method to detect its deletion. Using whole exome analysis of eight MM cell lines, we picked up 312 genes with biallelic deletions and/or variants with protein damaging. Gene annotation analysis revealed that 302 genes belong to the family genes of histone modifier, chromatin remodeling (especially mSWEI/SNF), transcription factors and their co-factors. We also detected several MM cells were resistant to HDAC-inhibitors. Since HDAC-inhibitors lead to growth arrest and differentiation through histone modifiers, they were not effective to MM cells without these factors. We also detected that several somatic variants detected by whole exome analysis were derived from germline, suggesting that these germline variants may be useful markers to detect MM susceptibility.

Free Research Field

人類遺伝学