Frequent aberration of the transforming growth factor-beta receptor II gene in cell lines but no apparent mutation in pre-invasive and invasive carcinomas of the uterine cervix

The type II transforming growth factor-beta (TGF-beta) receptor (RII) gene located at 3p22 plays an important role in regulating growth and differenti ation of epithelium, including that of the uterine cervix. Loss-of-function mutations of RII have frequently been found in gastrointestinal cancers, w ith a replication-error (RER) phenotype characterized by the presence of mi crosatellite instability (MI), In this study, genomic PCR, SSCP and DNA seq uencing were conducted to investigate the coding sequences of the RII gene in cell lines (n = 5) and tissues (n = 15) of squamous carcinomas of the ut erine cervix, Intragenic deletions were noted in 2 of 5 cervical-cancer cel l lines (ME180 and HeLa cells). However, no mutation, other than DNA polymo rphisms, was found in 15 cervical cancers with either alleleic loss at 3p22 (n = I I) or MI (n = 4), Further analysis of squamous intraepithelial lesi ons (SIL) with (n = 12) or without (n = 4) MI for the (A) lo change, a prot otypic mutation found in over 90% of RER-positive colon cancers, also showe d no aberration. Our study con eludes that the RII gene is frequently disru pted in cervical-cancer cell lines, but is rarely mutated in CC and SIL tis sues, including those showing MI or alleleic loss at 3p22, The underlined m echanism of genomic instability in CC and SIL may thus differ from that of colorectal cancer. The allelic loss at 3p22-24 in CC does not involve the c oding sequence of the RII gene. The non-coding sequence of RII or an uniden tified gene may be responsible for it. (C) 1999 Wiley-Liss. Inc.