Fine mapping and evaluation of candidate genes for cervical cancer on 11q23.
Fine mapping and evaluation of candidate genes for cervical cancer on 11q23.
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11q23 宫颈癌候选基因的精细定位和评估。
DOI：
10.1002/gcc.20151
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Rader,JanetS
中科院分区：
文献类型：
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作者：
Zhang,Zhengyan;Gerhard,DanielaS;Nguyen,Loan;Li,Jianduan;Traugott,Amber;Huettner,PhyllisC;Rader,JanetS
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 betweenD11S614andD11S4167. 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, andTRIM29) in the region and a proposed TSG (PPP2R1B) centromeric to the region were evaluated. The expression status ofUSP2, 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 ofPOU2F3andTRIM29was 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 inRNF26,USP2,TRIM29,POU2F3, orPPP2R1Bprobably are not important for cervical carcinogenesis. © 2005 Wiley‐Liss, Inc.
