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Title:
Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer | Breast Cancer Research
Description:
Introduction In breast cancer, gene expression analyses have defined five tumor subtypes (luminal A, luminal B, HER2-enriched, basal-like and claudin-low), each of which has unique biologic and prognostic features. Here, we comprehensively characterize the recently identified claudin-low tumor subtype. Methods The clinical, pathological and biological features of claudin-low tumors were compared to the other tumor subtypes using an updated human tumor database and multiple independent data sets. These main features of claudin-low tumors were also evaluated in a panel of breast cancer cell lines and genetically engineered mouse models. Results Claudin-low tumors are characterized by the low to absent expression of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response genes and cancer stem cell-like features. Clinically, the majority of claudin-low tumors are poor prognosis estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and epidermal growth factor receptor 2 (HER2)-negative (triple negative) invasive ductal carcinomas with a high frequency of metaplastic and medullary differentiation. They also have a response rate to standard preoperative chemotherapy that is intermediate between that of basal-like and luminal tumors. Interestingly, we show that a group of highly utilized breast cancer cell lines, and several genetically engineered mouse models, express the claudin-low phenotype. Finally, we confirm that a prognostically relevant differentiation hierarchy exists across all breast cancers in which the claudin-low subtype most closely resembles the mammary epithelial stem cell. Conclusions These results should help to improve our understanding of the biologic heterogeneity of breast cancer and provide tools for the further evaluation of the unique biology of claudin-low tumors and cell lines.
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Keywords {π}
claudinlow, breast, cell, tumors, cancer, expression, cells, pubmed, figure, data, article, tumor, subtype, luminal, lines, gene, normal, google, scholar, differentiation, basallike, genes, predictor, human, stem, samples, cas, subtypes, file, epithelial, additional, line, intrinsic, identified, features, unc, sumpt, central, mammary, molecular, showed, database, markers, analysis, high, set, perou, breastlike, masc, group,
Topics {βοΈ}
cd44+/cd24-/low/claudin-low profile increased cd44+/cd24-/low/mammosphere signature reported sum149pt cd49f+/epcam-/low-sorted subpopulation claudin-low centroid-based predictor mouse anti-vimentin igg1-ΞΊ sum149pt cd49f+/highepcam+-sorted subpopulation cd44+cd24-/low stem cell cd49f+/epcam-/low antigenic phenotypes anthracycline/taxane-based chemotherapy compared cd44+/cd24-/low-sorted cells cd44+/cd24-/low subpopulation obtained article download pdf cd49f+/epcam-/low sum149pt cells fluorescence-activated cell sorting epithelial cell-cell adhesion anthracycline/taxane-based chemotherapy claudin-low subtype reveals retinoblastoma tumour suppressor stem cells/tics/epithelial differentiation human claudin-low predictor mouse anti-human igg2a cell-type-specific responses claudin-low subtype classification claudin-low cell lines emt-inducing transcription factors claudin-low tumors versus gene expression profiles hypoxia-inducible factor-1a cd44+/cd24-/low cells claudin-low intrinsic subtype clear epcam-/low subpopulation expression profiles vary claudin-low tumor subtype stem cell-related markers human claudin-low tumors examine claudin-low tumors sigclust-defined claudin-low group claudin-low profile claudin-low breast tumors claudin-low tumors showed claudin-low gene cluster gene-expression-based predictors granulocyte-specific gene signatures claudin-low molecular subtype sum159pt-sorted cell fractions claudin-low samples identified luminal-restricted progenitor [cd49f+ claudin-low tumors identified supplementary figures s1-s10 undifferentiated claudin-low tumors
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headline:Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer
description:In breast cancer, gene expression analyses have defined five tumor subtypes (luminal A, luminal B, HER2-enriched, basal-like and claudin-low), each of which has unique biologic and prognostic features. Here, we comprehensively characterize the recently identified claudin-low tumor subtype. The clinical, pathological and biological features of claudin-low tumors were compared to the other tumor subtypes using an updated human tumor database and multiple independent data sets. These main features of claudin-low tumors were also evaluated in a panel of breast cancer cell lines and genetically engineered mouse models. Claudin-low tumors are characterized by the low to absent expression of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response genes and cancer stem cell-like features. Clinically, the majority of claudin-low tumors are poor prognosis estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and epidermal growth factor receptor 2 (HER2)-negative (triple negative) invasive ductal carcinomas with a high frequency of metaplastic and medullary differentiation. They also have a response rate to standard preoperative chemotherapy that is intermediate between that of basal-like and luminal tumors. Interestingly, we show that a group of highly utilized breast cancer cell lines, and several genetically engineered mouse models, express the claudin-low phenotype. Finally, we confirm that a prognostically relevant differentiation hierarchy exists across all breast cancers in which the claudin-low subtype most closely resembles the mammary epithelial stem cell. These results should help to improve our understanding of the biologic heterogeneity of breast cancer and provide tools for the further evaluation of the unique biology of claudin-low tumors and cell lines.
datePublished:2010-09-02T00:00:00Z
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Breast Cancer Cell Line
Intrinsic Subtype
Differentiation Hierarchy
SUM149PT Cell
Dual Positive Cell
Cancer Research
Oncology
Surgical Oncology
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headline:Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer
description:In breast cancer, gene expression analyses have defined five tumor subtypes (luminal A, luminal B, HER2-enriched, basal-like and claudin-low), each of which has unique biologic and prognostic features. Here, we comprehensively characterize the recently identified claudin-low tumor subtype. The clinical, pathological and biological features of claudin-low tumors were compared to the other tumor subtypes using an updated human tumor database and multiple independent data sets. These main features of claudin-low tumors were also evaluated in a panel of breast cancer cell lines and genetically engineered mouse models. Claudin-low tumors are characterized by the low to absent expression of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response genes and cancer stem cell-like features. Clinically, the majority of claudin-low tumors are poor prognosis estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and epidermal growth factor receptor 2 (HER2)-negative (triple negative) invasive ductal carcinomas with a high frequency of metaplastic and medullary differentiation. They also have a response rate to standard preoperative chemotherapy that is intermediate between that of basal-like and luminal tumors. Interestingly, we show that a group of highly utilized breast cancer cell lines, and several genetically engineered mouse models, express the claudin-low phenotype. Finally, we confirm that a prognostically relevant differentiation hierarchy exists across all breast cancers in which the claudin-low subtype most closely resembles the mammary epithelial stem cell. These results should help to improve our understanding of the biologic heterogeneity of breast cancer and provide tools for the further evaluation of the unique biology of claudin-low tumors and cell lines.
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Intrinsic Subtype
Differentiation Hierarchy
SUM149PT Cell
Dual Positive Cell
Cancer Research
Oncology
Surgical Oncology
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