title: Analysis of TGF-beta type I receptor for mutations and polymorphisms in head and neck cancers.
abstract: Transforming growth factor-beta receptor (TbetaR)-dependent signals are critical for cell growth and differentiation and are often disrupted during tumorigenesis. The entire coding region of TbetaR-I and flanking intron sequences from 30 head and neck carcinomas were examined for alterations using "Cold" SSCP and direct sequencing. No somatic point mutations were found in the TbetaR-I gene. In contrast, 14 polymorphic sequence changes were detected in TbetaR-I in 13 (43%) of the samples, including eight (27%) nucleotide alterations identified as polymorphisms in an exon-1 (GCG)(9) microsatellite repeat, a previously reported tumor susceptibility allele. A nine base pair deletion was found in 23% of the samples including five heterozygous and two homozygous deletions as well as single homozygous 12bp deletion. Additionally, six heterozygous polymorphisms in intronic sequences were determined, including one heterozygous C/A genotype at the +82 nucleotide position of the intron-5 intervening sequence (IVS), and five heterozygous G/A genotypes within intron-7 at the +24 nucleotide position. Exon-1 polymorphisms in the (GCG)(9) microsatellite region of the TbetaR-I gene and their association with head/neck cancers, suggest that development of these cancers may be a direct consequence of loss of responsiveness to TGF-beta mediated growth inhibition.
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Knobloch
authors.forename: M A
authors.initials: MA
authors.lastname: Lynch
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.forename: V L
authors.initials: VL
authors.lastname: DeGroff
authors.forename: B C
authors.initials: BC
authors.lastname: Casto
authors.forename: E M
authors.initials: EM
authors.lastname: Adams
authors.forename: K Y
authors.initials: KY
authors.lastname: Alam
authors.forename: J C
authors.initials: JC
authors.lastname: Lang
authors.forename: D E
authors.initials: DE
authors.lastname: Schuller
authors.forename: C M
authors.initials: CM
authors.lastname: Weghorst
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D018895:Microsatellite Repeats; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I