Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas

被引:51
作者
Senchenko, V
Liu, J
Braga, E
Mazurenko, N
Loginov, W
Seryogin, Y
Bazov, I
Protopopov, A
Kisseljov, FL
Kashuba, V
Lerman, MI
Klein, G
Zabarovsky, ER [1 ]
机构
[1] Karolinska Inst, Ctr Genom & Bioinformat, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden
[2] Russian Acad Sci, Ctr Bioengn, Moscow 117312, Russia
[3] Russian State Genet Ctr, Moscow 113545, Russia
[4] Russian Acad Med Sci, Blokhin Canc Res Ctr, Moscow 115478, Russia
[5] NCI, Canc Causing Genes Sect, Immunobiol Lab, Ctr Canc Res, Frederick, MD 21702 USA
[6] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia
关键词
quantitative real-time PCR; human chromosome 3p; tumor suppressor genes; NotI linking clone; loss of heterozygosity; cervical carcinoma;
D O I
10.1038/sj.onc.1206429
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We report chromosome 3p deletion mapping of 32 cervical carcinoma (CC) biopsies using 26 microsatellite markers located in frequently deleted 3p regions to detect loss of heterozygosity and homozygous loss. In addition, two STS markers (NLJ-003 and NL3-001) located in the 3p21.3 telomeric (3p21.3T) and 3p21.3 centromeric (3p21.3C) regions, respectively, were used for quantitative real-time PCR as TaqMan probes. We show that quantitative real-time PCR is reliable and sensitive and allows discriminating between 0, 1 and 2 marker copies per human genome. For the first time, frequent (five of 32 cases, i.e. 15.6%) homozygous deletions were demonstrated in CCs in both 3p21.3T and 3p21.3C regions. The smallest region homozygously deleted in 3p21.3C was located between D3S1568 (CACNA2D2 gene) and D3S4604 (SEMA3F gene) and contains 17 genes previously defined as lung cancer candidate Tumor suppressor genes (TSG(s)). The smallest region homozygously deleted in 3p21.3T was flanked by D3S1298 and NL1-024 (D3S4285), excluding DLEC1 and MYD88 as candidate TSGs involved in cervical carcinogenesis. Overall, this region contains five potential candidates, namely GOLGA4, APRG1, ITGA9, HYA22 and VILL, which need to be analysed. The data showed that aberrations of either NLJ-003 or NL3-001 were detected in 29 cases (90.6%) and most likely have a synergistic effect (P<0.01). The study also demonstrated that aberrations in 3p21.3 were complex and in addition to deletions, may involve gene amplification as well. The results strongly suggest that 3p21.3T and 3p21.3C regions harbor genes involved in the origin and/or development of CCs and imply that those genes might be multiple TSG(s).
引用
收藏
页码:2984 / 2992
页数:9
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