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

Transforming growth factor-beta receptor (T betaR)-dependent signals are cr itical for cell growth and differentiation and are often disrupted during t umorigenesis. The entire coding region of T betaR-I and flanking intron seq uences from 30 head and neck carcinomas were examined for alterations using "Cold" SSCP and direct sequencing. No somatic point mutations were found i n the T betaR-I gene. In contrast, 14 polymorphic sequence changes were det ected in T betaR-I in 13 (43%) of the samples, including eight (27%) nucleo tide alterations identified as polymorphisms in an exon-1 (GCG)(9) microsat ellite repeat, a previously reported tumor susceptibility allele. A nine ba se pair deletion was found in 23% of the samples including five heterozygou s and two homozygous deletions as well as single homozygous 12 bp deletion. Additionally, six heterozygous polymorphisms in intronic sequences were de termined, including one heterozygous C/A genotype at the +82 nucleotide pos ition of the intron-5 intervening sequence (IVS), and five heterozygous G/A genotypes within intron-7 at the +24 nucleotide position. Exon-1 polymorph isms in the (GCG)(9) microsatellite region of the T betaR-I gene and their association with head/neck cancers, suggest that development of these cance rs may be a direct consequence of loss of responsiveness to TGF-beta mediat ed growth inhibition. (C) 2001 Elsevier Science B.V. All rights reserved.