Clonal chromosome abnormalities in human breast carcinomas II. Thirty‐four cases with metastatic disease

Trent, Jeffrey M.; Yang, Jin‐Ming; Emerson, Julia; Dalton, William S.; McGee, Daniel; Massey, Kathy; Thompson, Floyd H.; Villar, Hugo V.

doi:10.1002/gcc.2870070403

Cited by 70 publications

(54 citation statements)

References 8 publications

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“…In several studies, chromosome 1q and 16q imbalances have been investigated separately: chromosome 1q gains have been found at any stage, [18][19][20] whereas chromosome 16q losses have been mostly detected in low and intermediately differentiated carcinoma 3,4 or in invasive lobular carcinoma. 21 Altogether, these data supported the hypothesis that low/intermediate-and high-grade breast carcinoma develop according to distinct pathways: chromosome 16q loss was proposed as a marker of a distinct genetic pathway in breast carcinoma development.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma

et al. 2004

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We applied comparative genomic hybridization (CGH) to 46 breast carcinoma samples, collected from 1993 to 1995, in order to detect chromosome 1q gains and 16q losses and to define whether samples showing both these alterations had distinct biopathologic features and different clinical outcome. A total of 22 samples (48%) had simultaneous chromosome 1q gain and 16q loss, which was always associated with other genetic changes. In total, 23 samples had various chromosome imbalances (including chromosome 1q gain independent of chromosome 16q loss and vice versa) and one sample did not show detectable alterations. Samples having chromosome 1q gain/16q loss were compared to the other samples with regard to neoplasm size, lymph-node status, histologic and nuclear grade, estrogen and progesterone receptor presence, Ki-67, pRB, Cyclin D1, Cyclin A, p53, p21 and p27 expression as detected by immunohistochemistry. The samples showing chromosome 1q gain/16q loss had high steroid hormone receptor expression (P ¼ 0.02), low cell growth fraction (Ki-67, P ¼ 0.03) and high p27 expression (Po0.001). No statistical correlation with disease-free survival and overall survival or response to hormonal therapy was found. We conclude that simultaneous chromosome 1q gain/16q loss is a frequent event in invasive breast cancer, which occurs in a subset of both intermediateand high-grade breast carcinomas. Although the final chromosome 1q and 16q imbalances might have originated from different chromosome alterations in low-and high-grade samples, the gene-dosage effect might be important in conferring peculiar biopathologic characteristics to this subset of samples. The cytogenetic and molecular mechanisms underlying these chromosome changes deserve further investigations.

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Section: Discussionmentioning

confidence: 99%

Simultaneous chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma

et al. 2004

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“…The early passage sporadic breast cancer cell lines were developed and maintained at the Arizona Cancer Center Cell Culture Core Facility. The UACC1179 and UACC2087 cells were derived from pleural effusions, while UACC893 was derived from a primary tumor (Meltzer et al, 1991;Thompson et al, 1993;Trent et al, 1993). MDA-MB-435 and MDA-MB-231 were maintained in RPMI 1640 containing 5% fetal bovine serum supplemented with 50 mg/ ml pen/strep.…”

Section: Cell Culture Adenoviral Infections and Drug Treatmentsmentioning

confidence: 99%

Mutant p53 and aberrant cytosine methylation cooperate to silence gene expression

et al. 2003

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p53 is an important transcriptional regulator that is frequently mutated in cancer. Gene-profiling experiments of breast cancer cells infected with wt p53 revealed both MASPIN and desmocollin 3 (DSC3) to be p53-target genes, even though both genes are silenced in association with aberrant cytosine methylation of their promoters. Despite the transcriptional repression of these genes by aberrant DNA methylation, restoration of p53 resulted in the partial reactivation of both genes. This reactivation is a result of wt p53 binding to its consensus DNA-binding sites within the MASPIN and DSC3 promoters, stimulating histone acetylation, and enhancing chromatin accessibility of their promoters. Interestingly, wt p53 alone did not affect the methylation status of either promoter, suggesting that p53 itself can partially overcome the repressive barrier of DNA methylation. Pharmacologic inhibition of DNA methylation with 5-aza-2 0 -deoxycytidine in combination with restoration of wt p53 status resulted in a synergistic reactivation of these genes to near-normal levels. These results suggest that cancer treatments that target both genetic and epigenetic facets of gene regulation may be a useful strategy towards the therapeutic transcriptional reprogramming of cancer cells.

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“…UACC3199 is an early passage sporadic breast cancer cell line derived from an infiltrating ductal carcinoma isolated from axillary lymph nodes. In this study, UACC3199 was passaged not more than 20 times and maintains the original genotype and phenotype of the primary tumor (21,22). Normal human mammary epithelial cells (HMEC) were purchased from Clonetics (San Diego, CA) and grown according to the manufacturer's instructions.…”

Section: Cell Culturementioning

confidence: 99%

Transcriptional repression of BRCA1 by aberrant cytosine methylation, histone hypoacetylation and chromatin condensation of the BRCA1 promoter

Rice¹

2000

Nucleic Acids Research

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BRCA1 expression is repressed by aberrant cytosine methylation in sporadic breast cancer. We hypothesized that aberrant cytosine methylation of the BRCA1 promoter was associated with the transcriptionally repressive effects of histone hypoacetylation and chromatin condensation. To address this question, we developed an in vitro model of study using normal cells and sporadic breast cancer cells with known levels of BRCA1 transcript to produce a 1.4 kb 5-methylcytosine map of the BRCA1 5′ CpG island. While all cell types were densely methylated upstream of -728 relative to BRCA1 transcription start, all normal and BRCA1 expressing cells were non-methylated downstream of -728 suggesting that this region contains the functional BRCA1 5′ regulatory region. In contrast, the non-BRCA1 expressing UACC3199 cells were completely methylated at all 75 CpGs. Chromatin immunoprecipitations showed that the UACC3199 cells were hypoacetylated at both histones H3 and H4 in the BRCA1 promoter compared to non-methylated BRCA1 expressing cells. The chromatin of the methylated UACC3199 BRCA1 promoter was inaccessible to DNA-protein interactions. These data indicate that the epigenetic effects of aberrant cytosine methylation, histone hypoacetylation and chromatin condensation act together in a discrete region of the BRCA1 5′ CpG island to repress BRCA1 transcription in sporadic breast cancer.

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Clonal chromosome abnormalities in human breast carcinomas II. Thirty‐four cases with metastatic disease

Cited by 70 publications

References 8 publications

Simultaneous chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma

Simultaneous chromosome 1q gain and 16q loss is associated with steroid receptor presence and low proliferation in breast carcinoma

Mutant p53 and aberrant cytosine methylation cooperate to silence gene expression

Transcriptional repression of BRCA1 by aberrant cytosine methylation, histone hypoacetylation and chromatin condensation of the BRCA1 promoter

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