In the present study, we analyzed 28
squamous cell carcinomas of the head and neck (SCCHN) for mutations in the coding region of TbetaR-II using 'Cold' SSCP and automatic
DNA sequencing analyses. Twenty-one percent (6/28) of the SCCHN examined contained TbetaR-II mutations compared with patient-matched normal tissues. These alterations included five missense mutations (A:T-->G:C transitions in
codons 250, 401, 448 and 488, and a G:C-->T:A transversion in
codon 373), and a 38-bp deletion between
nucleotides 1825 to 1862. In addition to these code-altering mutations, one case exhibited a silent mutation (A:T-->G:C transition in
codon 451) and three cases contained one of two potential population polymorphisms (
codons 354 and 389). In contrast to colon and
gastric cancers exhibiting
microsatellite instability (MI) or replication errors (RER+), no 'indirect' frameshift mutations were identified within a 10-bp
polyadenine repeat present in the TbetaR-II coding sequence. All of the mutations in the present study occurred within the highly conserved
serine/threonine kinase domain and represent the first report of such 'direct' TbetaR-II mutations in primary human
tumors. In addition, we analyzed a subset of SCCHN and corresponding normal samples for TbetaR-II
mRNA expression using semi-quantitative multiplex RT-PCR. Expression of TbetaR-II was decreased by 24% to 74% in 20 of 23 SCCHN (87%) compared with patient-matched normal tissues. Taken together, the results from this study suggest that alterations in the
nucleic acid sequence and
mRNA expression of TbetaR-II are prevalent events in the development of SCCHN, which may deregulate cell cycle control.