title: Novel microdeletion in the transforming growth factor beta type II receptor gene is associated with giant and large cell variants of nonsmall cell lung carcinoma.
abstract: Mutations in the tumor suppressor gene transforming growth factor beta (TGFB) Type II receptor (TGFBR2) are frequently found in many cancers with microsatellite instability, but are less common in lung cancer. In the present study, we looked for mutations in TGFBR2 in nonsmall cell lung carcinoma (NSCLC) cells and tissues. A novel homozygous microdeletion (c.492_507del) was identified in two cell lines derived from the same giant cell carcinoma (GCC) and was confirmed in the corresponding tumor tissues. Furthermore, a heterozygous c.492_507del was found in the germ-line of one patient, as well as in the other GCC cases and some large cell carcinomas (LCC) but not in other subtypes of NSCLC. The 16 bp-microdeletion introduced a premature stop codon at positions 590-592 of the cDNA, resulting in a truncated TGFBR2 protein with a mutated transmembrane domain and loss of kinase domain. The GCC cells were characterized as being unresponsive to TGFB induction both in growth inhibition and stimulation of extracellular matrix protein. Moreover, after the reconstitution of wild-type TGFBR2 expression, the sensitivity to TGFB was restored. Therefore, mutated TGFBR2 seems to play an important role in the abrogation of TGFB signal transduction in GCC cells.
authors.affiliation: The State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Jiu-Cun
authors.initials: JC
authors.lastname: Wang
authors.forename: Cheng-Chang
authors.initials: CC
authors.lastname: Su
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Xu
authors.forename: Le-Zhen
authors.initials: LZ
authors.lastname: Chen
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Hu
authors.forename: Gui-Ying
authors.initials: GY
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Bao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.forename: Song-Bin
authors.initials: SB
authors.lastname: Fu
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.forename: Chen-Qi
authors.initials: CQ
authors.lastname: Lu
authors.forename: Rong-Mei
authors.initials: RM
authors.lastname: Zhang
authors.forename: Z W
authors.initials: ZW
authors.lastname: Luo
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D018286:Carcinoma, Giant Cell / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II