MOLECULAR PATHOLOGY ON FOLLICULIN GENE ABNORMALITIES AND TUMORIGENESIS OF VARIOUS ORGANS

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08374
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Chiba University
• Principal Investigator: NAKATANI Yukio 千葉大学, 大学院医学研究院, 教授 (20137037)
• Co-Investigator(Kenkyū-buntansha): 古屋 充子 横浜市立大学, 医学部, 准教授 (10361445) ; 矢澤 卓也 獨協医科大学, 医学部, 教授 (50251054) ; 太田 聡 千葉大学, 医学部附属病院, 准教授 (90324342)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: バート・ホッグ・デュベ症候群 / フォリキュリン / 腎癌 / 肺癌 / 遺伝子解析 / 疫学

Outline of Final Research Achievements

Genetic, epidemiological and clinicopathological analyses were performed on 185 probands who were confirmed as BHD syndrome by genetic tests and their sibs with BHD syndrome-associated lesions, together forming the cohort of 477 subjects. As a result, Forty-five different mutation patterns were detected in FLCN. These included 3 cases of very rare small deletions of exons. Renal carcinomas developed in 35% of patients who were over 40 years old. Lung cancers, colon cancers and thyroid cancers occurred around 3% of patients. Adenocarcinoma, atypical adenomatous hyperplasia and multifocal micronodular pneumocyte hyperplasia-like lesion were seen as lung neoplasms; they commonly showed LOH of FLCN and invasive adenocarcinomas commonly showed mutations of EGFR and KRAS as well. Thyroid carcinoma and parotid adenoma resembled chromophobe renal cell carcinoma morphologically and harbored LOH of FLCN, suggesting a role of FLCN gene abnormalities in the tumorigenesis of these neoplasms.

Free Research Field

人体病理学