Showing papers by "Charles M. Perou published in 2001"

Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications

Abstract: The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome. A total of 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas, and four normal breast tissues were analyzed by hierarchical clustering. As reported previously, the cancers could be classified into a basal epithelial-like group, an ERBB2-overexpressing group and a normal breast-like group based on variations in gene expression. A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups, each with a distinctive expression profile. These subtypes proved to be reasonably robust by clustering using two different gene sets: first, a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and, second, a gene set that highly correlated with patient outcome. Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.

Diversity of gene expression in adenocarcinoma of the lung

Abstract: The global gene expression profiles for 67 human lung tumors representing 56 patients were examined by using 24,000-element cDNA microarrays. Subdivision of the tumors based on gene expression patterns faithfully recapitulated morphological classification of the tumors into squamous, large cell, small cell, and adenocarcinoma. The gene expression patterns made possible the subclassification of adenocarcinoma into subgroups that correlated with the degree of tumor differentiation as well as patient survival. Gene expression analysis thus promises to extend and refine standard pathologic analysis.

Towards a novel classification of human malignancies based on gene expression patterns.

Abstract: As a result of progress on the human genome project, approximately 19 000 genes have been identified and tens of thousands more tentatively identified as partial fragments of genes termed expressed sequence tags (ESTs). Most of these genes are only partially characterized and the functions of the vast majority are as yet unknown. It is likely that many genes that might be useful for diagnosis and/or prognostication of human malignancies have yet to be recognized. The advent of cDNA microarray technology now allows the efficient measurement of expression for almost every gene in the human genome in a single overnight hybridization experiment. This genomic scale approach has begun to reveal novel molecular-based sub-classes of tumours in breast carcinoma, colon carcinoma, lymphoma, leukaemia, and melanoma. In several instances, gene microarray analysis has already identified genes that appear to be useful for predicting clinical behaviour. This review discusses some recent findings using gene microarray technology and describes how this and related technologies are likely to contribute to the emergence of novel molecular classifications of human malignancies.

A Comparison of Gene Expression Signatures from Breast Tumors and Breast Tissue Derived Cell Lines

Abstract: Cell lines derived from human tumors have historically served as the primary experimental model system for exploration of tumor cell biology and pharmacology. Cell line studies, however, must be interpreted in the context of artifacts introduced by selection and establishment of cell lines in vitro. This complication has led to difficulty in the extrapolation of biology observed in cell lines to tumor biology in vivo. Modern genomic analysis tool like DNA microarrays and gene expression profiling now provide a platform for the systematic characterization and classification of both cell lines and tumor samples. Studies using clinical samples have begun to identify classes of tumors that appear both biologically and clinically unique as inferred from their distinctive patterns of expressed genes. In this review, we explore the relationships between patterns of gene expression in breast tumor derived cell lines to those from clinical tumor specimens. This analysis demonstrates that cell lines and tumor samples have distinctive gene expression patterns in common and underscores the need for careful assessment of the appropriateness of any given cell line as a model for a given tumor subtype.

Basal cell markers in breast cancer and uses thereof

Abstract: The invention provides a variety of reagents for use in the diagnosis and management of breast cancer. The invention utilizes cDNA microarray technology to identify genes whose expression profile across a large group of tumor samples correlates with that of cytokeratin 5 and cytokeratin 17, markers for basal cells of the normal mammary lactation gland. The invention demonstrates that tumors that express cytokeratin 5/6 and/or 17 have a poor prognosis relative to tumors overall. The invention provides basal marker genes and their expression products and uses of these genes for diagnosis of breast cancer and for identification of therapies for breast cancer. In particular, the invention provides basal marker genes including cadherin3, matrix metalloproteinase 14, and cadherin EGF LAG seven-pass G-type receptor 2. The invention provides antibodies to the polypeptides expressed by these genes and methods of use thereof.

Microarrays in primary breast cancer--lessons from chemotherapy studies.

Abstract: Current development in molecular techniques has extended the opportunities to explore genetic alterations in malignant tissue. There is a need to improve prognostication and, in particular, to understand the mechanisms of treatment resistance in different tumours. Gene analyses by microarrays allow concomitant analyses of several genes in concert, providing new opportunities for tumour classification and understanding of key biological disturbances. This paper outlines our continuing studies exploring prognostic and, we hope, predictive factors in breast cancer therapy.

Methods of classifying, diagnosing, stratifying and treating cancer patients and their tumors

Abstract: The invention provides a variety of reagents for use in the diagnosis and management of breast cancer. The invention utilizes cDNA microarray technology to identify genes whose expression profile across a large group of tumor samples correlates with that of cytokeratin 5 and cytokeratin 17, markers for basal cells of the normal mammary lactation gland. The invention demonstrates that tumors that express cytokeratin 5/6 and/or 17 have a poor prognosis relative to tumors overall. The invention provides basal marker genes and their expression products and uses of these genes for diagnosis of breast cancer and for identification of therapies for breast cancer. In particular, the invention provides basal marker genes including cadherin3, matrix metalloproteinase 14, and cadherin EGF LAG seven-pass G-type receptor 2. The invention provides antibodies to the polypeptides expressed by these genes and methods of use thereof.