Fine mapping and evaluation of candidate genes for cervical cancer on 11q23.
We previously showed that loss of heterozygosity (LOH) at 11q23 is a common genetic alteration in cervical cancer (CC) and that it correlates with extensive invasion of lymph-vascular spaces. In the current study, we looked for allelic loss in paired normal/tumor genomic DNA from 121 cervical tumors by using 20 well-mapped microsatellite markers on 11q. LOH at one or more loci was observed in 81 (66.9%) tumors. The deletion patterns in tumors are complex. However, at least three LOH islands could be defined between D11S614 and D11S4167. We also genotyped 11 CC cell lines and analyzed the results using the homozygosity mapping-of-deletions method. Five of the 11 cell lines showed continuous homozygosity that extended through 11q23.3-11q24.1. We used a candidate-gene approach to screen candidate tumor-suppressor genes (TSGs) that were localized in that region. Intragenic changes in the entire coding sequence of four candidate genes (RNF26, USP2, POU2F3, and TRIM29) in the region and a proposed TSG (PPP2R1B) centromeric to the region were evaluated. The expression status of USP2, POU2F3, TRIM29, and another proposed TSG that is telomeric to the region (BCSC1) also was examined. We identified previously described single-nucleotide polymorphisms (SNPs), several novel variants, and three rare SNPs in the five candidate genes. Decreased expression of POU2F3 and TRIM29 was found in some cervical tumors and CC cell lines. Our results indicate that a major region of LOH in cervical cancer exists within a 3.6-Mb stretch of DNA on 11q23.3-q24.1 and that somatic mutations in RNF26, USP2, TRIM29, POU2F3, or PPP2R1B probably are not important for cervical carcinogenesis.
Zhang
Zhengyan
Z
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Gerhard
Daniela S
DS
Nguyen
Loan
L
Li
Jianduan
J
Traugott
Amber
A
Huettner
Phyllis C
PC
Rader
Janet S
JS
D000230:Adenocarcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D045744:Cell Line, Tumor; D002874:Chromosome Mapping / Q000379:methods; D002880:Chromosomes, Human, Pair 11; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics*