title: Alterations of Fas-pathway genes associated with nodal metastasis in non-small cell lung cancer.
abstract: Many types of cancer cells are resistant to Fas-mediated apoptosis by several mechanisms, including the mutations of the genes involved in Fas-mediated apoptosis. In this study, to explore the possibility that the mutations of the genes involved in the proximal pathway of Fas-mediated apoptosis (Fas, FADD, caspase 8 and caspase 10) are involved in cancer metastasis, we have analysed somatic mutation and deletion of these genes in 80 non-small cell lung cancers (NSCLCs) with (n=43) and without (n=37) metastasis to the regional lymph nodes. We found 12 mutations (four Fas, four FADD, and four caspase 10 mutations) in 11 of 80 NSCLCs (13.8%). Interestingly, of these mutations, most mutations (10 out of 12) were detected in the NSCLCs with metastasis, and the frequency in the metastasis lesions (23%) was higher than that in the primary lesions of the NSCLCs without metastasis (5.4%). Furthermore, transfection study revealed that the tumor-derived mutants have decreased apoptosis inductions compared to the wild types. These data suggest that the inactivating mutations of the genes in the proximal pathway of Fas-mediated apoptosis may lead to a decreased cancer cell death and play a role in the metastasis of NSCLC.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Shin
authors.forename: Hong Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Song
authors.forename: Young Sill
authors.initials: YS
authors.lastname: Kim
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Su Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Shi Nae
authors.initials: SN
authors.lastname: Lee
authors.forename: Jik Young
authors.initials: JY
authors.lastname: Park
authors.forename: Jong Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Wensua
authors.initials: W
authors.lastname: Xiao
authors.forename: Keon Hyon
authors.initials: KH
authors.lastname: Jo
authors.forename: Young Pil
authors.initials: YP
authors.lastname: Wang
authors.forename: Kyo Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Park
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics*; D017931:DNA Primers; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D019014:fas Receptor / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017931:DNA Primers; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; C506438:CASP10 protein, human