Study: JGAS00000000115




TitleBHD-associated kidney cancer
AbstractBackground 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 for energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, how FLCN-deficiency leads to renal tumorigenesis is unclear. Results Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations (CNV) of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. Somatic mutation analysis revealed BHD-associated kidney cancer has quite few common mutations in specific genes; however, chromatin remodeling genes in total were frequently mutated in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis revealed that glycolysis, pentose phosphate pathway and lipid metabolism were upregulated whereas the rate of beta oxydation and TCA cycle is decreased in BHD-associated kidney cancer compared to normal adjacent kidney. Conclusions BHD-associated kidney cancer displays a unique molecular characteristics which is totally different from that of sporadic kidney cancer, providing the mechanistic insight into tumorigenesis under FLCN deficiency as well as the foundation for the development of novel therapeutics for kidney cancer.
Study Type
Study TypeTumor vs. Matched-Normal


TitleProject for Development of Innovative Research on Cancer Therapeutics (P-DIRECT)
AgencyMinistry of Education, Culture, Sports, Science and Technology, Japan (MECSST, JP)
Grant ID0

Study Link

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Study Attribute

NBDC Numberhum0070
Registration date2017-08-18
Submitting organizationYokohama City University
Principal InvestigatorMasahiro Yao
Molecular Data TypeWhole Exome Sequencing
PlatformHiSeq 2000/2500
Primary PhenotypeCancer
Study Inclusion/Exclusion CriteriaBHD syndrome
Disease TypeNeoplasms
Accession Title Dataset type Data objects Policy
JGAD00000000125 Exome of 29 BHD-associated kidney cancer Exome sequencing 44 JGAP00000000004