Identification of genetic alterations in the TGF beta type II receptor gene promoter

Modifications in the control sequences of tumor suppressor genes have been found to play a role in the activation or inactivation of these genes and m ay play an important role in tumorigenesis. For example, hypermethylation o f CpG islands and promoter polymorphisms have been found to be involved in transcriptional repression. A decrease in the levels of expression of one s uch tumor suppressor gene, the TGF beta type H receptor (T R-H), has been a ssociated with increased tumorigenicity in a number of human tumors. Geneti c alterations have been described in several tumor types in the coding regi on of this gene. However, no comprehensive search for genetic alterations i n the T betaR-II promoter has been reported. Genetic alterations in the pro moter of the T betaR-II gene could inhibit binding of putative regulatory f actors. For example, we have reported a A-364-G alteration in the T betaR-I I promoter, which results in decreased transcriptional activity. In this st udy, we analyzed the 1.0 kb region upstream of the T betaR-II transcription al start site and found genetic alterations in 46% of the head and neck squ amous cell carcinoma (SqCC) samples examined. The most frequent alteration was a G-875-A alteration, present in 41.6% of the samples. Analysis of norm al healthy individuals showed a similar frequency of this alteration, sugge sting that alterations within the T betaR-II promoter are unlikely to accou nt for the decreased expression of T betaR-II in head and neck SqCC. (C) 20 01 Elsevier Science B.V. All rights reserved.