Molecular Genetic analysis and Tumorigenesis of Birt-Hogg-Dube syndrome in Japan

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10600
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Yokohama City University
• Principal Investigator: YAO Masahiro 横浜市立大学, 医学研究科, 教授 (00260787)
• Co-Investigator(Kenkyū-buntansha): 中井川 昇 横浜市立大学, 医学部, 准教授 (00237207) ; 古屋 充子 横浜市立大学, 医学部, 准教授 (10361445) ; 蓮見 壽史 横浜市立大学, 附属病院, 助教 (40749876)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: バート・ホッグ・デュベ 症候群 / 遺伝性腎腫瘍 / FLCN遺伝子 / BHD症候群

Outline of Final Research Achievements

We analyzed germline mutation and clinicopathologic characteristics of 312 patients from 120 Birt-Hogg-Dube syndrome (BHD) families. A total of 31 different FLCN sequence variants, including 3 hotspots, were identified. Almost all patients presented with pulmonary cysts, however, cutaneous manifestations were relatively weak. The incidence of RCCs in over the age of 40 was 34.8%. We conducted whole-exome sequencing analysis as well as metabolite analysis in BHD associated kidney cancers. Copy number variations (CNV) are considerably different from those in sporadic cases. Very few somatic variants were commonly observed, however, variants in chromatin remodeling genes were frequently observed. Metabolite analysis revealed metabolic reprogramming towards upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency.

Free Research Field

泌尿器科学