Genetic and Expression Aberrations of E3 Ubiquitin Ligases in Human Breast Cancer

Chen, Ceshi; Seth, Arun; Aplin, Andrew E.

doi:10.1158/1541-7786.mcr-06-0182

Cited by 60 publications

(53 citation statements)

References 197 publications

(145 reference statements)

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“…Protein degradation through the ubiquitin proteasome system regulates such processes as cell cycle, apoptosis, transcription, protein trafficking, signaling, DNA replication and repair, and angiogenesis; defects in this pathway have been well documented in breast cancer (26). Well known examples are the deregulation of the ubiquitin ligases BRCA1, BRCA2, BARD1, and MDM2 in subsets of human breast cancers (27). Although dactylidin has been little studied in cancer, it's membership in a class of genes including BRCA1, BRCA2, and BARD1 suggest that it could play a role in tumorigenesis of breast or other malignancies.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33

Gold

Kirchhoff²,

Стефанов

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

268

195

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We performed a three-phase genome-wide association study (GWAS) using cases and controls from a genetically isolated population, Ashkenazi Jews (AJ), to identify loci associated with breast cancer risk. In the first phase, we compared allele frequencies of 150,080 SNPs in 249 high-risk, BRCA1/2 mutation-negative AJ familial cases and 299 cancer-free AJ controls using 2 and the Cochran-Armitage trend tests. In the second phase, we genotyped 343 SNPs from 123 regions most significantly associated from stage 1, including 4 SNPs from the FGFR2 region, in 950 consecutive AJ breast cancer cases and 979 age-matched AJ controls. We replicated major associations in a third independent set of 243 AJ cases and 187 controls. We obtained a significant allele P value of association with AJ breast cancer in the FGFR2 region (P ‫؍‬ 1.5 ؋ 10 ؊5 , odds ratio (OR) 1.26, 95% confidence interval (CI) 1.13-1.40 at rs1078806 for all phases combined). In addition, we found a risk locus in a region of chromosome 6q22.33 (P ‫؍‬ 2.9 ؋ 10 ؊8 , OR 1.41, 95% CI 1.25-1.59 at rs2180341). Using several SNPs at each implicated locus, we were able to verify associations and impute haplotypes. The major haplotype at the 6q22.33 locus conferred protection from disease, whereas the minor haplotype conferred risk. Candidate genes in the 6q22.33 region include ECHDC1, which encodes a protein involved in mitochondrial fatty acid oxidation, and also RNF146, which encodes a ubiquitin protein ligase, both known pathways in breast cancer pathogenesis.genomics ͉ mapping ͉ disease ͉ predisposition ͉ SNP C ohort and twin studies have indicated that 5-15% of incident breast cancer cases result from autosomal-dominant cancer susceptibility (1-5). However, only Ϸ40% of the familial aggregation of breast cancers can be explained by mutations in BRCA1, BRCA2, or other identified cancer susceptibility genes (6). Attempts to use linkage strategies to localize other genes associated with an inherited predisposition to cancer have been hampered by genetic heterogeneity, decreased penetrance, and chance clustering (7-12). Candidate gene studies in multiplex kindreds affected by breast cancer have implicated rare variants of CHEK2, ATM, BRIP1, and PALB2 in the subset of families lacking BRCA mutations, but in most cases, the rarity and small effect sizes of these associations have precluded clinical application (13). Association studies of biologically plausible candidate genes have identified low-penetrance susceptibility alleles in pathways of carcinogen metabolism, inflammation and immune response, DNA metabolism and DNA repair as well as other known oncogenes and tumor suppressor genes (14-17). Most recently, two groups have carried out genome-wide association studies (GWAS) of selected kindreds and unselected individuals affected by breast cancer (18,19). These studies have implicated a locus near FGFR2 as associated with an Ϸ1.2-fold increased risk of the disease. To add to the potential power of the GWAS approach, we have proposed and validated the use of a genet...

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33

Gold

Kirchhoff²,

Стефанов

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

268

195

View full text Add to dashboard Cite

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“…Monoubiquitination occurs after attachment of a single ubiquitin to a single lysine of a substrate protein. Following monoubiquitination, a second ubiquitin molecule can be conjugated to the first one through an isopeptide bond between Gly 76 of the second ubiquitin molecule and the -NH 2 groups of one of the seven lysines (Lys 6 (23)(24)(25). Abnormal accumulation or hyperactive degradation of these regulatory proteins may be associated with carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Protein Profiling of Human Breast Tumor Cells Identifies Novel Biomarkers Associated with Molecular Subtypes

Gonçalvès

Charafe-Jauffret²,

Bertucci³

et al. 2008

Molecular & Cellular Proteomics

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We identified two of them as a carboxyl terminus-truncated form of ubiquitin and S100A9. In a small series of frozen human breast tumors, we confirmed that carboxyl terminus-truncated ubiquitin is observed in primary breast samples, and our results suggest its higher expression in luminal-like tumors. S100A9 up-regulation was found as part of the transcriptionally defined basal-like cluster in DNA microarrays analysis of human tumors. S100A9 association with basal subtypes as well as its poor prognosis value was demonstrated on a series of 547 tumor samples from early breast cancer deposited in a tissue microarray. Our study shows the potential of integrated genomics and proteomics profiling to improve molecular knowledge of complex tumor phenotypes and identify biomarkers with valuable diagnostic or prognostic values.

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“…E3s play critical roles because they control the substrate specificity. Accumulating evidence suggests that genetic and expression alteration of E3s contributes to breast carcinogenesis (Chen et al, 2006). histone sumoylation as a component of the group of modifications that appear to govern chromatin structure and function to mediate transcriptional repression and gene silencing (Shiio et al, 2003).…”

Section: The Other Histone Modifications In Breast Cancermentioning

confidence: 99%

Histone Modification and Breast Cancer

Luo¹,

Guo²,

Guo³

et al. 2011

Breast Cancer - Focusing Tumor Microenvironment, Stem Cells and Metastasis

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Genetic and Expression Aberrations of E3 Ubiquitin Ligases in Human Breast Cancer

Cited by 60 publications

References 197 publications

Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33

Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33

Protein Profiling of Human Breast Tumor Cells Identifies Novel Biomarkers Associated with Molecular Subtypes

Histone Modification and Breast Cancer

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