Exonic expression profiling of breast cancer and benign lesions: a retrospective analysis

André, Fabrice; Michiels, Stefan; Dessen, Philippe; Scott, Véronique; Suciu, Voïchita; Uzan, Catherine; Lazar, Vladimir; Lacroix, Ludovic; Vassal, Gilles; Spielmann, M.; Vielh, Philippe; Delaloge, Suzette

doi:10.1016/s1470-2045(09)70024-5

Cited by 58 publications

(50 citation statements)

References 37 publications

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“…15 In some cancers, the upregulation of specific splice variants amounts to a "molecular signature" for neoplasia. 16,17 Here, we investigate the relationship of each CRNDE transcript to colorectal neoplasia. In addition, we define the boundaries and features of the CRNDE locus through exon microarray analyses, 5′-RACE, and transcript-specific RT-PCR assays.…”

Section: Introductionmentioning

confidence: 99%

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

Pedersen²,

et al. 2011

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An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia differentially expressed (gene symbol CRNDE), is activated early in colorectal neoplasia. The locus is unrelated to any known protein-coding gene. Microarray analysis of 454 tissue specimens (discovery) and 68 previously untested specimens (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas and adenocarcinomas. These findings were confirmed and extended by exon microarray studies and RT-PCR assays. CRNDE transcription start sites were identified in CaCo2 and HCT116 cells by 5′-RACE. The major transcript isoforms in colorectal cancer (CRC) cell lines and colorectal tissue are CRNDE-a, -b, -d, -e, -f, -h, and -j. Except for CRNDE-d, the known CRNDE splice variants are upregulated in neoplastic colorectal tissue; expression levels for CRNDE-h alone demonstrate a sensitivity of 95% and specificity of 96% for adenoma versus normal tissue. A quantitative RT-PCR assay measuring CRNDE-h RNA levels in plasma was (with a threshold of 2 -ΔCt = 2.8) positive for 13 of 15 CRC patients (87%) but only 1 of 15 healthy individuals (7%). We conclude that individual CRNDE transcripts show promise as tissue and plasma biomarkers, potentially exhibiting high sensitivity and specificity for colorectal adenomas and cancers.

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Section: Introductionmentioning

confidence: 99%

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

Pedersen²,

et al. 2011

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“…For instance, metabolism, immune system, and epigenetics have been reported as targetable in oncology. Looking for novel pathways involved in cancer progression, we previously identified spliceosome assembly components as the most enriched pathway in breast cancer samples, when compared with benign lesions (1).…”

Section: Introductionmentioning

confidence: 99%

Targeting the Deregulated Spliceosome Core Machinery in Cancer Cells Triggers mTOR Blockade and Autophagy

et al. 2013

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The spliceosome is a large ribonucleoprotein complex that guides pre-mRNA splicing in eukaryotic cells. Here, we determine whether the spliceosome could constitute an attractive therapeutic target in cancer. Analysis of gene expression arrays from lung, breast, and ovarian cancers datasets revealed that several genes encoding components of the core spliceosome composed of a heteroheptameric Sm complex were overexpressed in malignant disease as compared with benign lesions and could also define a subset of highly aggressive breast cancers. siRNA-mediated depletion of SmE (SNRPE) or SmD1 (SNRPD1) led to a marked reduction of cell viability in breast, lung, and melanoma cancer cell lines, whereas it had little effect on the survival of the nonmalignant MCF-10A breast epithelial cells. SNRPE or SNRPD1 depletion did not lead to apoptotic cell death but autophagy, another form of cell death. Indeed, induction of autophagy was revealed by cytoplasmic accumulation of autophagic vacuoles and by an increase in both LC3 (MAP1LC3A) protein conversion and the amount of acidic autophagic vacuoles. Knockdown of SNRPE dramatically decreased mTOR mRNA and protein levels and was accompanied by a deregulation of the mTOR pathway, which, in part, explains the SNRPE-dependent induction of autophagy. These findings provide a rational to develop new therapeutic agents targeting spliceosome core components in oncology. Cancer Res; 73(7); 2247-58. Ó2013 AACR.

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“…Since these probes are specific to known or evidenced splice events, previously undescribed exon skipping events and alternative splice site acceptors and donors will not be detected with this approach. This platform was used in a study that examined both gene expression and exon usage in benign and malignant breast tissue [12]. Comparing malignant to benign tissue defined 956 over-expressed exons in genes whose expression did not change.…”

Section: Techniques To Profile Alternative Splicingmentioning

confidence: 99%

“…Profiling of 120 BrCs and 45 benign lesions on a genome-wide splice array (Splice Array, ExonHit) was used to define a molecular classifier for BrC diagnosis and to identify which exons are differentially expressed in breast cancer compared to benign lesions [12]. This study identified 37,858 exon probe sets, 18,794 junction probe sets, and 3,733 genes that were differently expressed in malignant and benign lesions.…”

Section: Global Analysis Of Splice Variants In Breast Cancermentioning

confidence: 99%

“…From this data, a 1228-probe-set was defined that served as a molecular classifier for BrC. Pathway analysis of genes over-expressed in BrC samples compared to benign breast lesions identified 11 of 15 genes involved in spliceosome assembly [12]. Triple-negative (ER, PR and Her2/neu negative) or Her2-overexpressing BrCs were more likely to over-express spliceosome components.…”

Section: Global Analysis Of Splice Variants In Breast Cancermentioning

confidence: 99%

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Alternative Splicing in Prostate and Breast Cancer

Watson¹,

Watson²

2010

TOCJ

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UAb stract: Alternative splicing of mRNA precursors allows the synthesis of multiple mRNAs from a single primary transcript, thus contributing to proteomic diversity in higher eukaryotes. Multiple studies demonstrate that alternative splicing patterns are altered during cancer progression. Several different mechanisms can contribute to changes in the regulation of alternative splicing. This report will provide an overview of how splicing microarrays and large-scale sequencing are being used to identify splicing changes in breast and prostate cancer. Global analyses of splice variants have identified cancer-specific splice variant patterns that have potential use as biomarkers and potentially have prognostic value as well as may represent novel therapeutic targets. A description of specific splice variants with differential expression in these cancers and their possible functions will be presented.

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Exonic expression profiling of breast cancer and benign lesions: a retrospective analysis

Cited by 58 publications

References 37 publications

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

Targeting the Deregulated Spliceosome Core Machinery in Cancer Cells Triggers mTOR Blockade and Autophagy

Alternative Splicing in Prostate and Breast Cancer

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