From Description to Causality: Mechanisms of Gene Expression Signatures in Cancer

Adler, Adam S.; Chang, Howard Y.

doi:10.4161/cc.5.11.2798

Cited by 19 publications

(11 citation statements)

References 32 publications

(49 reference statements)

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“…Taken together, these results suggest that MYC amplification may play an important biological role in the later stages of tumour progression, 13 in particular in the activation of a transcriptional programme that promotes the development of breast cancer metastasis. [38][39][40] In conclusion, this study shows that although MYC amplification is heterogeneous in breast carcinomas, it can be reliably and rapidly assessed on tissue microarrays by means of CISH using a combination of a gene specific probe for MYC and a centromeric probe for chromosome 8. However, more than one N MYC is heterogeneously amplified in breast cancer.…”

Section: Discussionmentioning

confidence: 74%

MYCamplification in breast cancer: a chromogenic in situ hybridisation study

et al. 2006

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Aims: To analyse the correlation between MYC amplification and various clinicopathological features and outcome in a cohort of 245 patients with invasive breast carcinoma treated with surgery followed by anthracycline-based chemotherapy. Given the high prevalence of MYC amplification in tumours of BRCA1 mutation carriers and the similarities between these and sporadic ''basal-like'' carcinomas, the prevalence of MYC amplification in ''basal-like'' breast carcinomas was investigated. Methods: MYC gene copy number was assessed on tissue microarrays containing duplicate cores of 245 invasive breast carcinomas by means of chromogenic in situ hybridisation using SpotLight C-MYC amplification probe and chromosome 8 centromeric probe (CEP8). Signals were evaluated at 4006 magnification; 30 morphologically unequivocal neoplastic cells in each core were counted for the presence of the gene and CEP8 probes. Results: Amplification was defined as a MYC:CEP8 ratio .2. Signals for both MYC and CEP8 were assessable in 196/245 (80%) tumours. MYC amplification was found in 19/196 cases (9.7%) and was not associated with tumour size, histological grade, positivity for oestrogen receptor, progesterone receptor, HER2, epidermal growth factor, cytokeratins 14, 5/6 and 17, MIB1 or p53. Only 4% of basal-like carcinomas showed MYC amplification, compared to 8.75% and 10.7% of luminal and HER2 tumours respectively. On univariate analysis, MYC amplification displayed a significant association with shorter metastasis-free and overall survival and proved to be an independent prognostic factor on multivariate survival analysis. Conclusion: MYC amplification is not associated with ''basal-like'' phenotype and proved to be an independent prognostic factor for breast cancer patients treated with anthracycline-based chemotherapy.

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Section: Discussionmentioning

confidence: 74%

MYCamplification in breast cancer: a chromogenic in situ hybridisation study

et al. 2006

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“…[44][45][46][47] Nevertheless, some expression profiling analyses 48 support a correlation between Myc levels and poor breast cancer outcome. In addition, an analytical approach integrating expression and copy number profiles 49,50 has indicated that the so-called "wound response" expression signature previously associated with poor overall survival and increased risk of metastasis in breast cancer 51 can be correlated with a coordi- nate amplification of Myc and Cops5 (a gene encoding one of the subunits of the Cop9 signalosome).…”

Section: Myc In Normal Human Breast and Breast Cancermentioning

confidence: 99%

Notch, Myc and Breast Cancer

Efstratiadis

Szabolcs²,

Klinakis³

2007

Cell Cycle

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“…In recent years, the magnitude and frequency of transcriptional and chromosomal changes that occur in human cancers have been quantified by DNA microarrays on a comprehensive genomic scale. Correlative analyses of these data have revealed robust associations among gene-expression patterns, copy number alterations, and clinical features of disease (1)(2)(3)(4)(5)(6)(7) and may provide a discovery-based framework for uncovering genes with important pathophysiologic roles in cancer (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

RCP is a human breast cancer–promoting gene with Ras-activating function

Zhang¹,

Liu²,

Datta³

et al. 2009

J. Clin. Invest.

113

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Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most cases, the causal or contributing genetic components remain poorly understood. Here, we utilized microarray informatics to identify candidate oncogenes potentially contributing to aggressive breast cancer behavior. We identified the Rab-coupling protein RCP (also known as RAB11FIP1), which is located at a chromosomal region frequently amplified in breast cancer (8p11-12) as a potential candidate. Overexpression of RCP in MCF10A normal human mammary epithelial cells resulted in acquisition of tumorigenic properties such as loss of contact inhibition, growth-factor independence, and anchorage-independent growth. Conversely, knockdown of RCP in human breast cancer cell lines inhibited colony formation, invasion, and migration in vitro and markedly reduced tumor formation and metastasis in mouse xenograft models. Overexpression of RCP enhanced ERK phosphorylation and increased Ras activation in vitro. As these results indicate that RCP is a multifunctional gene frequently amplified in breast cancer that encodes a protein with Ras-activating function, we suggest it has potential importance as a therapeutic target. Furthermore, these studies provide new insight into the emerging role of the Rab family of small G proteins and their interacting partners in carcinogenesis.

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From Description to Causality: Mechanisms of Gene Expression Signatures in Cancer

Cited by 19 publications

References 32 publications

MYCamplification in breast cancer: a chromogenic in situ hybridisation study

MYCamplification in breast cancer: a chromogenic in situ hybridisation study

Notch, Myc and Breast Cancer

RCP is a human breast cancer–promoting gene with Ras-activating function

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