Intratumoral heterogeneity of FLCN somatic mutations in gastric and colorectal cancers
FLCN gene encoding folliculin protein is a cytoplasmic guanine exchange factor associated with Birt-Hogg-Dubé (BHD) syndrome, the clinical manifestations of which include multiple tumors and pulmonary cysts . Folliculin interacts with AMP-activated protein kinase (AMPK) and regulates energy metabolism in cells . Activation of AMPK-related mTOR pathway may be responsible for tissue lesions . In BHD syndrome, skin and kidney tumors are common, but colon tumors have also been reported in some individuals with BHD . Frameshift mutations in the C8 mononucleotide repeat in exon 8 are the most common inactivating mutation in BHD individuals [1, 2]. The same frameshift mutations of FNCL are detected in sporadic colorectal cancer (CRC) with high microsatellite instability (MSI-H) (16% (5/32) of one study, 0% (0/5) of the other study) [3, 4]. Together, FLCN is considered a tumor suppressor gene (TSG).
Approximately 10–20% of gastric (GC) and CRC are MSI-H cancers that...
This work was supported by a grant from National Research Foundation of Korea (2019R1A5A2027588).
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