Identification and validation of an ERBB2 gene expression signature in breast cancers

Bertucci, François; Borie, N.; Ginestier, Christophe; Groulet, Agnès; Charafe-Jauffret, Emmanuelle; Adélaı̈de, José; Geneix, Jeannine; Bachelart, Loïc; Finetti, Pascal; Koki, Alane; Hermitte, Fabienne; Hassoun, Jacques; Debono, Stéphane; Viens, Patrice; Fert, Vincent; Jacquemier, Jocelyne; Birnbaum, Daniel

doi:10.1038/sj.onc.1207361

Cited by 119 publications

(118 citation statements)

References 48 publications

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“…However, correlation between gene expression and mutation has not been observed in many solid tumor types, with the exception of tumors with dominant activating mutations, such as sarcomas with KIT mutations (Allander et al, 2001) or characteristic translocations (Schaefer et al, 2004), melanomas with BRAF mutations (Pavey et al, 2004), hereditary breast TC FV FV FV FV FV FV CT FV FV CT # of genes per class THY004 THY048 THY049 THY073 THY098 THY140 THY149 THY152 THY164 THY185 Genes used by the classifier were selected by the other 40 tumors with known mutations from a set of 15 266 probe-sets that were not redundant for the genes (assessed via unigene IDs). For each of the 11 PCs, the predicted mutation based on the number of genes used by the classifier is shown, as well as the morphologic type of each tumor (Hedenfalk et al, 2001) and ovarian carcinoma (Jazaeri et al, 2002), and breast carcinomas that overexpress ERBB2 (Bertucci et al, 2004) or have mutated TP53 (Sorlie et al, 2001). A KRAS2 expression signature of lung adenocarcinomas, not apparent from human tumors alone, was recently derived by combining expression profiles of human and mouse tumors (Sweet-Cordero et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis

et al. 2005

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Thyroid cancer poses a significant clinical challenge, and our understanding of its pathogenesis is incomplete. To gain insight into the pathogenesis of papillary thyroid carcinoma, transcriptional profiles of four normal thyroids and 51 papillary carcinomas (PCs) were generated using DNA microarrays. The tumors were genotyped for their common activating mutations: BRAF V600E point mutation, RET/PTC1 and 3 rearrangement and point mutations of KRAS, HRAS and NRAS. Principal component analysis based on the entire expression data set separated the PCs into three groups that were found to reflect tumor morphology and mutational status. By combining expression profiles with mutational status, we defined distinct expression profiles for the BRAF, RET/PTC and RAS mutation groups. Using small numbers of genes, a simple classifier was able to classify correctly the mutational status of all 40 tumors with known mutations. One tumor without a detectable mutation was predicted by the classifier to have a RET/PTC rearrangement and was shown to contain one by fluorescence in situ hybridization analysis. Among the mutation-specific expression signatures were genes whose differential expression was a direct consequence of the mutation, as well as genes involved in a variety of biological processes including immune response and signal transduction. Expression of one mutationspecific differentially expressed gene, TPO, was validated at the protein level using immunohistochemistry and tissue arrays containing an independent set of tumors. The results demonstrate that mutational status is the primary determinant of gene expression variation within these tumors, a finding that may have clinical and diagnostic significance and predicts success for therapies designed to prevent the consequences of these mutations.

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Section: Discussionmentioning

confidence: 99%

Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis

et al. 2005

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“…The construction, analysis of tissue microarrays and immunohistochemistry were performed as previously described (Ginestier et al, 2002;Bertucci et al, 2004). A consecutive series of 547 women with localized invasive breast carcinomas treated at the Institut Paoli-Calmettes between 1981 and 1999 was studied using TMA.…”

Section: Immunolocalizationmentioning

confidence: 99%

Junctional recruitment of mammalian Scribble relies on E-cadherin engagement

et al. 2005

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Members of the LAP protein family, LET-413 inCaenorhabditis elegans, Scribble in Drosophila melanogaster, and Erbin, Lano, Densin-180 and hScrib in mammals, have conserved structural features. LET-413 and Scribble are junctional proteins involved in establishing and maintaining epithelial cell polarity. scribble also behaves as a neoplastic tumor suppressor gene. We show here that, in epithelial cells, hScrib is recruited at cell-cell junctions in an E-cadherin-dependent manner as shown by calcium switch assays in MDCK cells, re-expression of E-cadherin in MDA-231 cells treated by 5-Aza-2 0 -deoxycytidine (5Aza), and siRNA experiments. hScrib is restricted at the basolateral membrane of epithelial cells by its LRR domain, and is enriched in Triton X-100-insoluble fractions. In breast cancers, most lobular tumors did not express hScrib and E-cadherin while ductal tumors had a less frequent downregulation of hScrib. Our data provide additional insights on the modalities of recruitment of hScrib at the cell-cell junctions, and establish a potential link between the E-cadherin and hScrib tumor suppressors.

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“…Genes included in the basal cluster were also tested, and their negative prognostic role was confirmed in several hundreds of tumors: crystallin alpha B (118), cytokeratins 5 and 17 (119), and annexin A8 (120). Using DNA microarrays, we identified a gene expression signature associated with ERBB2 status (121). We then used TMAs (ϳ250 tumors) to validate at the protein level the positive correlation of GATA4 and Ki67 with ERBB2.…”

Section: Tissue Microarray Studiesmentioning

confidence: 99%

Proteomics of Breast Cancer

Bertucci

Birnbaum

Gonçalvès

2006

Molecular & Cellular Proteomics

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Progresses in screening, early diagnosis, prediction of aggressiveness and of therapeutic response or toxicity, and identification of new targets for therapeutic will improve survival of breast cancer. These progresses will likely be accelerated by the new proteomic techniques. In this review, we describe the different techniques currently applied to clinical samples of breast cancer and the most important results obtained with the two most popular proteomic approaches in translational research (tissue microarrays and SELDI-TOF). Molecular & Cellular Proteomics 5:1772-1786, 2006.Worldwide, breast cancer is one of the most frequent and deadly cancers. Although the survival of patients has increased over the last decades in relation with screening programs and postoperative adjuvant systemic therapies (hormone therapy and chemotherapy), many patients die from metastatic relapse. Breast cancer is a complex disease. Accumulation of numerous and often unknown molecular alterations causes cell proliferation, genetic instability, and acquisition of an increasingly invasive and resistant phenotype. The combinatorial origin and the heterogeneity of malignant cells and the variability of the host background create molecularly distinct subgroups of tumors endowed with different phenotypes and clinical outcomes. This heterogeneity is only partially apprehended by the clinicopathological parameters currently used by clinicians, hampering the selection of the most appropriate diagnostic or therapeutic strategy for each case. In addition, current cytotoxic drugs do not differentiate between cancerous and normal cells, causing sometimes disastrous adverse effects. Major efforts aim at characterizing the heterogeneity of the disease by defining more reliable diagnostic/prognostic factors and at developing molecular therapies selectively targeting the tumor cells.For some decades, the study of molecular alterations has successfully elucidated some mechanisms of mammary oncogenesis and identified key genes such as ERBB2, TP53, CCND1, BRCA1, and BRCA2. It has also allowed considerable therapeutic progress by targeting hormonal receptors and ERBB2/HER2 receptor. Today high throughput molecular typing provides an unprecedented opportunity to tackle the combinatory aspect and the complexity of breast cancer. A combination of markers (molecular signature) will probably be more sensitive and specific than a single molecular marker to reflect the actual heterogeneity of disease; more reliable for screening, diagnosis, prognosis, and prediction of therapeutic response; and more useful to find new therapeutic targets. The first large scale techniques applied to the cancer field were DNA microarrays for mRNA expression profiling (1). Several studies have demonstrated the clinical potential of this approach, notably by identifying new biologically relevant and prognostic subclasses of breast cancer unidentifiable by conventional means (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). With the recent development of similar technologies at the DNA...

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Identification and validation of an ERBB2 gene expression signature in breast cancers

Cited by 119 publications

References 48 publications

Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis

Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis

Junctional recruitment of mammalian Scribble relies on E-cadherin engagement

Proteomics of Breast Cancer

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