High resolution mapping of chromosome 6 deletions in cervical cancer.

Мазуренко, Н. Н.; Attaleb, Mohammed; Gritsko, Tatyana; Semjonova, L. A.; Павлова, Л. С.; Sakharova, Olga V.; Kisseljov, F. L.

doi:10.3892/or.6.4.859

Cited by 35 publications

(41 citation statements)

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“…According to LOH and CGH data (Kisseljov et al, 1996;Rader et al, 1996Rader et al, , 1998Lazo, 1999;Mazurenko et al, 1999;Matthews et al, 2000) chromosome arms 3p, 6p and 11q were most frequently affected in squamous CC of the uterine cervix. Moreover, 3p and 6p were also involved at the early precancer stages and during progression of cervical intraepithelial neoplasia to invasive cervical cancer (Larson et al, 1997b;Wistuba et al, 1997;Fouret et al, 1998;Guo et al, 1998Guo et al, , 2000Guo et al, , 2001Umayahara et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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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 (Po0.01). 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).

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Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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“…18 and marker D6S281 at 6q27. 18 Reactions were cycled in a MJ Research PTC100 thermal cycler (Watertown, MA). Two rounds of a touchdown PCR was used.…”

Section: Analysis Of Lohmentioning

confidence: 99%

Loss of heterozygosity on chromosome arms 3p and 6q in microdissected adenocarcinomas of the uterine cervix and adenocarcinoma in situ

Acevedo

Henríquez

Emmert‐Buck

et al. 2002

Cancer

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BACKGROUNDDespite the increasing frequency of adenocarcinomas of the uterine cervix, little is known regarding inactivation of tumor suppressor genes (TSGs) in this tumor type. The authors analyzed loss of heterozygosity (LOH) in 36 carcinomas of the cervix with glandular differentiation, and 5 adenocarcinoma in situ in 40 patients.METHODSThe authors analyzed samples using laser capture microdissection from archival material and DNA amplified with microsatellite markers on the following loci: 3p14.2 (D3S1234, D3S1300), 3p21.3 (D3S1029, D3S1447), 3p22‐24 (D3S1537, D3S1351), 6q21‐23.3 (D6S250), 6q25.1 (ESR), 6q25.2 (D6S255), 8p21 (D8S136, D8S1820), 13q12.3 (D13S220, D13S267), 17q21 (D17S579, D17S855). Eight additional markers spanning the short arm of chromosome 3 (3p12‐p25) and six spanning the long arm of chromosome 6 (6q11‐q27) were studied in the cases showing LOH to further define the deletion intervals.RESULTSThe frequency of allelic loss in cancers was chromosome 3p: 49% (p14.2: 35%, p21.3: 23%, p22‐24: 41%), 6q: 48% (q21‐23.1: 39%, q25.1: 45%, q25.2: 7%), 13q: 22%, 17q: 6%, and 8p: 18%. On chromosome arm 3p, the authors' data suggest at least two discrete areas of deletion: a proximal area between markers D3S1234 (p12) and D3S1766 (p14.2‐14.3), and a second distal interval, telomeric from marker D3S4623 (p21.3). On chromosome 6q, the deletion area is between marker D6S300 (q22) and D6S255 (q25.2). Two of five preneoplastic lesions showed LOH on chromosome arm 3p, and two five showed allelic loss on chromosome arm on 6q, suggesting the genes might be inactivated early in cervical tumorigenesis.CONCLUSIONSThe authors have identified three chromosomal regions that may harbor TSGs involved in the development/progression of adenocarcinomas of the uterine cervix, 3p12‐14.2, 3p21.3‐pter, and 6q22‐25.2. Deletions also were detected in adenocarcinoma in situ, suggesting the genes may be inactivated early in cervical tumorigenesis. Cancer 2002;94:793–802. © 2002 American Cancer Society.DOI 10.1002/cncr.10275

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“…The human LATS1 gene has been localized to chromosome 6q24-25 (4). A frequent loss of heterozygosity (LOH) at this locus has been reported in ovarian (5,6), cervical (7) and breast cancers (8 -10). Overexpression of LATS1 causes G 2 -M arrest through the inhibition of CDC2 kinase activity in breast cancer cell line in vitro (11).…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of LATS1 and LATS2 mRNA Expression by Promoter Hypermethylation and Its Association with Biologically Aggressive Phenotype in Human Breast Cancers

Takahashi

Miyoshi²,

Takahata³

et al. 2005

Clinical Cancer Research

268

215

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Purpose: LATS1 and LATS2 are tumor suppressor genes implicated in the regulation of cell cycle. Methylation status of the promoter regions of these genes as well as its correlation with their mRNA levels were studied in human breast cancers. Correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics of breast tumors were also studied.Experimental Design: Methylation status of promoter regions of LATS1 and LATS2 was studied by a methylationspecific PCR and mRNA expression levels of LATS1 and LATS2 were determined by a real-time PCR assay in 30 breast cancers. In addition, correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics was studied in 117 breast cancers.Results: Methylation-specific PCR showed that of 30 tumors, LATS1 promoter region was hypermethylated in 17 tumors (56.7%) and LATS2 promoter region was hypermethylated in 15 (50.0%) tumors. LATS1 mRNA levels in breast tumors with hypermethylation (2.15 F F 0.37, mean F F SE) were significantly (P < 0.01) lower than those without hypermethylation (6.09 F F 1.38), and LATS2 mRNA levels in breast tumors with hypermethylation (1.42 F F 0.66) were also significantly (P < 0.01) lower than those without hypermethylation (3.10 F F 1.00). The decreased expression of LATS1 or LATS2 mRNA was significantly associated with a large tumor size, high lymph node metastasis, and estrogen receptor and progesterone receptor negativity. Furthermore, the decreased expression of LATS1 mRNA, but not LATS2 mRNA, was significantly (P < 0.05) associated with a poor prognosis.Conclusions: Hypermethylation of the promoter regions of LATS1 and LATS2 likely plays an important role in the down-regulation of their mRNA levels in breast cancers, and breast cancers with a decreased expression of LATS1 or LATS2 mRNA levels have a biologically aggressive phenotype.

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High resolution mapping of chromosome 6 deletions in cervical cancer.

Cited by 35 publications

References 0 publications

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

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

Loss of heterozygosity on chromosome arms 3p and 6q in microdissected adenocarcinomas of the uterine cervix and adenocarcinoma in situ

Down-Regulation of LATS1 and LATS2 mRNA Expression by Promoter Hypermethylation and Its Association with Biologically Aggressive Phenotype in Human Breast Cancers

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