title: Deletion mapping using quantitative real-time PCR identifies two distinct 3p21.3 regions affected in most cervical carcinomas.
abstract: 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).
authors.affiliation: Microbiology and Tumor Biology Center, Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, 17177 Sweden.
authors.forename: Vera
authors.initials: V
authors.lastname: Senchenko
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Eleonora
authors.initials: E
authors.lastname: Braga
authors.forename: Natalia
authors.initials: N
authors.lastname: Mazurenko
authors.forename: Witaly
authors.initials: W
authors.lastname: Loginov
authors.forename: Yury
authors.initials: Y
authors.lastname: Seryogin
authors.forename: Igor
authors.initials: I
authors.lastname: Bazov
authors.forename: Alexei
authors.initials: A
authors.lastname: Protopopov
authors.forename: Fedor L
authors.initials: FL
authors.lastname: Kisseljov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kashuba
authors.forename: Michael I
authors.initials: MI
authors.lastname: Lerman
authors.forename: George
authors.initials: G
authors.lastname: Klein
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Zabarovsky
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D005260:Female; D018628:Gene Dosage; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D002583:Uterine Cervical Neoplasms / Q000235:genetics*