title: Mutational analysis of the transforming growth factor beta receptor type I gene in primary non-small cell lung cancer.
abstract: Transforming growth factor-beta receptor-dependent signals are critical for cell growth and differentiation and are often disrupted during tumorigenesis. The entire coding region of TGFbetaRI and flanking intron sequences from 53 primary non-small cell lung cancer (NSCLC) tissues were examined for alterations using SSCP and direct sequencing. No somatic point mutations other than two silent mutations and a polymorphism were found in the TGFbetaRI gene. The two silent mutations located at codon 344 (AAT to AAC) and codon 406 (TTA to CTA), respectively, and the polymorphism was at the 24th base of intron 7 (G to A). To investigate whether the presence of this polymorphism is associated with NSCLC, we determined its allele distribution in all the 53 carcinomas and 89 normal controls. Interestingly, we found that the subjects with homozygous genotype A/A displayed more than 3-fold increased risk of developing NSCLC than the common wild genotype G/G. As the first report, the present study showed that TGFbetaRI gene is not a frequent site of spontaneous mutational inactivation while the detected polymorphism is frequent in the pathogenesis of NSCLC.
authors.affiliation: Laboratory of Population and Quantitative Genetics, The State Key Laboratory of Genetic Engineering, Institute of Genetics, Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai 200433, P.R. China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Zhang
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Fei
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Qi
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Jiu-Cun
authors.initials: JC
authors.lastname: Wang
authors.forename: Rong-Mei
authors.initials: RM
authors.lastname: Zhang
authors.forename: Shi-Heng
authors.initials: SH
authors.lastname: Tao
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Chen
authors.forename: Ze-Wei
authors.initials: ZW
authors.lastname: Luo
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I