Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in cervical cancer.
OBJECTIVE
PTEN/MMAC1, a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be homozygously deleted or 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 heterozygosity in cervical cancer.


METHODS
We examined 50 primary cervical carcinoma specimens using a PCR-based assay followed by SSCP and direct sequencing. The genomic DNA was also confirmed by Southern blot analysis.


RESULTS
All specimens except one, which has a 7-base deletion, showed a negative result. Among them, 30 randomly selected cases and their paired noncancerous tissue were further screened using nested RT-PCR. Six of 30 cervical cancerous tissues had aberrant transcripts. However, 4 of the matched noncancerous 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 detected in 1 of 50 cervical cancers analyzed indicating that aberrant PTEN/MMAC1 function is an uncommon event in the development of cervix cancers. However, similar to studies with the TSG101 gene, screening for aberrant transcripts of PTEN/MMAC1 with nested RT-PCR may detect transcripts, which, although 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.
Su
T H
TH
Division of Molecular Medicine, China Medical College Hospital, Taichung, Taiwan.
Chang
J G
JG
Perng
L I
LI
Chang
C P
CP
Wei
H J
HJ
Wang
N M
NM
Tsai
C H
CH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human