Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in cervical cancer

Objective. PTEN/MMAC1, a candidate tumor suppressor gene located at chromos ome 10q23.3, was recently identified and found to be homozygously deleted o r mutated in several different types of human tumors. The aim of this study is to determine whether PTEN/ MMAC1 is a target for 10q loss of heterozygo sity in cervical cancer. Method. We examined 50 primary cervical carcinoma specimens using a PCR-bas ed assay followed by SSCP and direct sequencing. The genomic DNA was also c onfirmed by Southern blot analysis, Results. All specimens except one, which has a 7-base deletion, showed a ne gative result. Among them, 30 randomly selected cases and their paired nonc ancerous tissue were further screened using nested RT-PCR. Six of 30 cervic al cancerous tissues had aberrant transcripts. However, 4 of the matched no ncancerous tissues also had aberrant transcripts. Southern blot analysis of the entire genomic DNA did not reveal any evidence of gene alteration. Conclusions. Sequence abnormalities in the PTEN/MMAC1 gene were only detect ed in 1 of 50 cervical cancers analyzed indicating that aberrant PTEN/MMAC1 function is an uncommon event in the development of cervix cancers. Howeve r, similar to studies with the TSG101 gene, screening for aberrant transcri pts of PTEN/MMAC1 with nested RT-PCR may detect transcripts, which, althoug h they vary from the normal size, may not be related to oncogenesis as they are also frequently found in normal tissues of the same patient. (C) 2000 Academic Press.