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A Novel Subset of Human Tumors That Simultaneously Overexpress Multiple E2F-responsive Genes Found in Breast, Ovarian, and Prostate Cancers.

Shackney SE, Chowdhury SA, Schwartz R - Cancer Inform (2014)

Bottom Line: Reasoning that overexpression of multiple E2F-responsive genes might be a useful marker for RB1 dysfunction, we compiled a list of E2F-responsive genes from the literature and evaluated their expression in publicly available gene expression microarray data of patients with breast cancer, serous ovarian cancer, and prostate cancer.A core group of about 30 E2F-responsive genes were overexpressed in all three cancer types.Thus, it appears that disorders of the Rb/E2F axis can arise at multiple organ sites and produce tumors that simultaneously overexpress multiple E2F-responsive genes.

View Article: PubMed Central - PubMed

Affiliation: President and CEO, Intelligent Oncotherapeutics Incorporated, Pittsburgh, PA, USA.

ABSTRACT
Reasoning that overexpression of multiple E2F-responsive genes might be a useful marker for RB1 dysfunction, we compiled a list of E2F-responsive genes from the literature and evaluated their expression in publicly available gene expression microarray data of patients with breast cancer, serous ovarian cancer, and prostate cancer. In breast cancer, a group of tumors was identified, each of which simultaneously overexpressed multiple E2F-responsive genes. Seventy percent of these genes were concerned with cell cycle progression, DNA repair, or mitosis. These E2F-responsive gene overexpressing (ERGO) tumors frequently exhibited additional evidence of Rb/E2F axis dysfunction, were mostly triple negative, and preferentially overexpressed multiple basal cytokeratins, suggesting that they overlapped substantially with the basal-like tumor subset. ERGO tumors were also identified in serous ovarian cancer and prostate cancer. In these cancer types, there was no evidence for a tumor subset comparable to the breast cancer basal-like subset. A core group of about 30 E2F-responsive genes were overexpressed in all three cancer types. Thus, it appears that disorders of the Rb/E2F axis can arise at multiple organ sites and produce tumors that simultaneously overexpress multiple E2F-responsive genes.

No MeSH data available.


Related in: MedlinePlus

A conceptual model for the evolutionary development of ERGO tumors qualitatively describing a governing hypothesis to explain the results of the paper in terms of relationships between the related but distinct categories of ERGO, triple-negative, basal-like, and BRCA1 tumors.
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f4-cin-suppl.5-2014-089: A conceptual model for the evolutionary development of ERGO tumors qualitatively describing a governing hypothesis to explain the results of the paper in terms of relationships between the related but distinct categories of ERGO, triple-negative, basal-like, and BRCA1 tumors.

Mentions: Figure 4 presents a model for breast cancer evolution consistent with the various findings of this study and intended to summarize their possible implications for breast cancer development and progression. Basal-like tumors are presumed to arise mostly from HER2 nonamplified and ER-negative precursors, and ERGO tumors develop from basal-like precursors. This is based on the findings by PCA that the tumor subset that consists mostly of basal-like tumors also includes most ERGO tumors and that PCA using E2F-responsive genes only separates the ERGO tumors from the non-ERGO basal-like tumors (see Fig. 2). A small group of ERGO tumors identified only by the entropy minimization method do not overexpress cytokeratins or alternative basal-like markers and is presumed not to overlap with the basal-like subset. Two-thirds of BRCA1-mutated breast cancers are ERGO tumors, and almost all the remaining BRCA1 tumors are grouped with the basal-like tumors. Since ERGO tumors represent a more advanced evolutionary state than basal-like tumors, it is reasonable to suppose that BRCA1-mutated tumors undergo the transition from basal-like to ERGO cancers as they evolve. This remains to be shown directly. Preliminary data in ovarian cancer and prostate cancer suggest that the basal-like to ERGO transition might not be a prominent feature of ERGO tumors that arise at other organ sites.


A Novel Subset of Human Tumors That Simultaneously Overexpress Multiple E2F-responsive Genes Found in Breast, Ovarian, and Prostate Cancers.

Shackney SE, Chowdhury SA, Schwartz R - Cancer Inform (2014)

A conceptual model for the evolutionary development of ERGO tumors qualitatively describing a governing hypothesis to explain the results of the paper in terms of relationships between the related but distinct categories of ERGO, triple-negative, basal-like, and BRCA1 tumors.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4221091&req=5

f4-cin-suppl.5-2014-089: A conceptual model for the evolutionary development of ERGO tumors qualitatively describing a governing hypothesis to explain the results of the paper in terms of relationships between the related but distinct categories of ERGO, triple-negative, basal-like, and BRCA1 tumors.
Mentions: Figure 4 presents a model for breast cancer evolution consistent with the various findings of this study and intended to summarize their possible implications for breast cancer development and progression. Basal-like tumors are presumed to arise mostly from HER2 nonamplified and ER-negative precursors, and ERGO tumors develop from basal-like precursors. This is based on the findings by PCA that the tumor subset that consists mostly of basal-like tumors also includes most ERGO tumors and that PCA using E2F-responsive genes only separates the ERGO tumors from the non-ERGO basal-like tumors (see Fig. 2). A small group of ERGO tumors identified only by the entropy minimization method do not overexpress cytokeratins or alternative basal-like markers and is presumed not to overlap with the basal-like subset. Two-thirds of BRCA1-mutated breast cancers are ERGO tumors, and almost all the remaining BRCA1 tumors are grouped with the basal-like tumors. Since ERGO tumors represent a more advanced evolutionary state than basal-like tumors, it is reasonable to suppose that BRCA1-mutated tumors undergo the transition from basal-like to ERGO cancers as they evolve. This remains to be shown directly. Preliminary data in ovarian cancer and prostate cancer suggest that the basal-like to ERGO transition might not be a prominent feature of ERGO tumors that arise at other organ sites.

Bottom Line: Reasoning that overexpression of multiple E2F-responsive genes might be a useful marker for RB1 dysfunction, we compiled a list of E2F-responsive genes from the literature and evaluated their expression in publicly available gene expression microarray data of patients with breast cancer, serous ovarian cancer, and prostate cancer.A core group of about 30 E2F-responsive genes were overexpressed in all three cancer types.Thus, it appears that disorders of the Rb/E2F axis can arise at multiple organ sites and produce tumors that simultaneously overexpress multiple E2F-responsive genes.

View Article: PubMed Central - PubMed

Affiliation: President and CEO, Intelligent Oncotherapeutics Incorporated, Pittsburgh, PA, USA.

ABSTRACT
Reasoning that overexpression of multiple E2F-responsive genes might be a useful marker for RB1 dysfunction, we compiled a list of E2F-responsive genes from the literature and evaluated their expression in publicly available gene expression microarray data of patients with breast cancer, serous ovarian cancer, and prostate cancer. In breast cancer, a group of tumors was identified, each of which simultaneously overexpressed multiple E2F-responsive genes. Seventy percent of these genes were concerned with cell cycle progression, DNA repair, or mitosis. These E2F-responsive gene overexpressing (ERGO) tumors frequently exhibited additional evidence of Rb/E2F axis dysfunction, were mostly triple negative, and preferentially overexpressed multiple basal cytokeratins, suggesting that they overlapped substantially with the basal-like tumor subset. ERGO tumors were also identified in serous ovarian cancer and prostate cancer. In these cancer types, there was no evidence for a tumor subset comparable to the breast cancer basal-like subset. A core group of about 30 E2F-responsive genes were overexpressed in all three cancer types. Thus, it appears that disorders of the Rb/E2F axis can arise at multiple organ sites and produce tumors that simultaneously overexpress multiple E2F-responsive genes.

No MeSH data available.


Related in: MedlinePlus