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  • Analysis of TGF-beta type I receptor for mutations and polymorphisms in head and neck cancers.

Analysis of TGF-beta type I receptor for mutations and polymorphisms in head and neck cancers.

Mutation research (2001-07-27)
T J Knobloch, M A Lynch, H Song, V L DeGroff, B C Casto, E M Adams, K Y Alam, J C Lang, D E Schuller, C M Weghorst
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.