BHD-associated kidney cancer exhibits unique molecular characteristics and a wide variety of variants in chromatin remodeling genes | Zendy

Hisashi Hasumi | Zendy; Mitsuko Furuya | Zendy; Kenji Tatsuno | Zendy; Shogo Yamamoto | Zendy; Masaya Baba | Zendy; Yukiko Hasumi | Zendy; Yasuhiro Isono | Zendy; Kae Suzuki | Zendy; Ryosuke Jikuya | Zendy; Shinji Otake | Zendy; Kentaro Muraoka | Zendy; Kimito Osaka | Zendy; Narihiko Hayashi | Zendy; Kazuhide Makiyama | Zendy; Yasuhide Miyoshi | Zendy; Keiichi Kondo | Zendy; Noboru Nakaigawa | Zendy; Takashi Kawahara | Zendy; Koji Izumi | Zendy; Junichi Teranishi | Zendy; Yasushi Yumura | Zendy; Hiroji Uemura | Zendy; Yoji Nagashima | Zendy; Adam R. Metwalli | Zendy; Laura S. Schmidt | Zendy; Hiroyuki Aburatani | Zendy; W. Marston Linehan | Zendy; Masahiro Yao | Zendy

Open Access

BHD-associated kidney cancer exhibits unique molecular characteristics and a wide variety of variants in chromatin remodeling genes

Author(s) -

Hisashi Hasumi,

Mitsuko Furuya,

Kenji Tatsuno,

Shogo Yamamoto,

Masaya Baba,

Yukiko Hasumi,

Yasuhiro Isono,

Kae Suzuki,

Ryosuke Jikuya,

Shinji Otake,

Kentaro Muraoka,

Kimito Osaka,

Narihiko Hayashi,

Kazuhide Makiyama,

Yasuhide Miyoshi,

Keiichi Kondo,

Noboru Nakaigawa,

Takashi Kawahara,

Koji Izumi,

Junichi Teranishi,

Yasushi Yumura,

Hiroji Uemura,

Yoji Nagashima,

Adam R. Metwalli,

Laura S. Schmidt,

Hiroyuki Aburatani,

W. Marston Linehan,

Masahiro Yao

Publication year - 2018

Publication title -

human molecular genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.811

H-Index - 276

eISSN - 1460-2083

pISSN - 0964-6906

DOI - 10.1093/hmg/ddy181

Subject(s) - biology , folliculin , carcinogenesis , kidney cancer , cancer , kidney , cancer research , genetics , gene

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer, which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming toward upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics that are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.

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