Loss of heterozygosity at microsatellite markers from region p11-21 of chromosome 8 in microdissected breast tumor but not in peritumoral cells

Charafe‐Jauffret, Emmanuelle; Moulin, Jean-Francois; Ginestier, Christophe; Bechlian, Didier; Conte, Nathalie; Geneix, Jeannine; Adélaı̈de, José; Noguchi, Tetsuro; Hassoun, Jacques; Jacquemier, Jocelyne; Birnbaum, Daniel

doi:10.3892/ijo.21.5.989

Cited by 9 publications

(8 citation statements)

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“…Lentivirus‐mediated expression of LSM1 , EIF4EBP1 , C8orf4 , PPAPDC1B , ZNF703 , RAB11FIP1 , BAG4 , and FGFR1 in MCF10A cells demonstrated a role for BAG4 , LSM1 , and C8orf4 but not RAB11FIP1 and PPAPDC1B in induction of transformed phenotypes (Yang et al,2006). TACC1 was overexpressed in three of three cell lines with amplification (Ray et al,2004) and induced transformation of mouse fibroblasts (Still et al,1999). More recently, in a mouse mammary transgenic model, it was shown to regulate positively the RAS and phosphatidylinositol 3‐kinase (PI3K) pathways to promote RAS‐mediated transformation and prevent apoptosis induced by PI3K pathway inhibition (Cully et al,2005).…”

Section: Discussionmentioning

confidence: 99%

“…Losses of distal 8p are reported in many epithelial cancers (Birnbaum et al,2003). The complexity of changes has led to the proposal that there is selection pressure for loss of more than one TSG (Takle and Knowles,1996; Charafe‐Jauffret et al,2002; Cooke et al,2008; Gorringe et al,2009). In breast cancer, a model with at least two TSG locations, one near the tip (possibly ARHGEF10 ) and one just distal to a breakpoint cluster in 8p12 (possibly NRG1 ; Chua et al,2009) have been proposed.…”

Section: Discussionmentioning

confidence: 99%

“…Attempts to pinpoint a minimal region of loss, and thus a tumor suppressor gene (TSG) location, have shown more than one minimal region in UC (Takle and Knowles,1996; Choi et al,2000; Adams et al,2005b) and in breast cancer (Charafe‐Jauffret et al,2002). Breakpoint studies have shown a variety of breakpoints in 8p, with clusters reported in NRG1 in breast cancer, and also in pancreas, lungs, and ovarian cancer (Adelaide et al,2003; Huang et al,2004).…”

Section: Introductionmentioning

confidence: 99%

“…This pattern of 8p distal loss, often accompanied by amplification of proximal 8p, has been shown in breast cancer frequently to involve complex cytogenetic changes (Pole et al,2006). At least four separate amplicons have been recognized in breast cancer (Gelsi‐Boyer et al,2005; Kwek et al,2009), whereas complex losses suggest the need to lose more than one TSG (Takle and Knowles,1996; Charafe‐Jauffret et al,2002; Cooke et al,2008; Gorringe et al,2009).…”

Section: Introductionmentioning

confidence: 99%

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High‐resolution analysis of genomic alteration on chromosome arm 8p in urothelial carcinoma

Williams

Platt

Hurst

et al. 2010

Genes Chromosomes & Cancer

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Loss of chromosome arm 8p, sometimes in combination with amplification of proximal 8p, is found in urothelial carcinoma (UC) and other epithelial cancers and is associated with more advanced tumor stage. We carried out array comparative genomic hybridization on 174 UC and 33 UC cell lines to examine breakpoints and copy number. This was followed by a detailed analysis of the cell lines using fluorescence in situ hybridization (FISH) and, in some cases, M-FISH, to refine breakpoints and determine translocation partners, heterozygosity analysis, and analysis of expression of selected genes. We showed an overall pattern of 8p loss with reduced heterozygosity and reduced gene expression. Amplification was seen in some samples and shown in the cell line JMSU1 to correlate with overexpression of ZNF703, ERLIN2, PROSC, GPR124, and BRF2. Apart from the centromere, no single breakpoint was overrepresented, and we postulate that frequent complex changes without consistent breakpoints reflect the need for alterations of combinations of genes. The region around 2 Mb, which was homozygously deleted in one cell line and includes the gene ARHGEF10 and the micro-RNA hsa-mir-596, is one candidate tumor suppressor gene region.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High‐resolution analysis of genomic alteration on chromosome arm 8p in urothelial carcinoma

Williams

Platt

Hurst

et al. 2010

Genes Chromosomes & Cancer

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“…Interstitial deletions of chromosome 8p occur at a high frequency in a range of different cancers (1)(2)(3)(4)(5)(6)(7), and linkage studies indicate the breast cancer gene BRCA3 may reside on this arm (8,9). Our studies of the region 8p11.2 in a series of prostate cancers (10), squamous cell head and neck cancers (11), and colorectal carcinomas (12) have shown frequent interstitial deletions in these different tumor types and an association between 8p11.2 deletion and local invasion (10,12).…”

Section: Introductionmentioning

confidence: 99%

The Wnt Antagonist sFRP1 in Colorectal Tumorigenesis

Caldwell¹,

Jones²,

Gensberg³

et al. 2004

Cancer Research

263

192

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Regions of the short arm of chromosome 8 are deleted frequently in a range of solid tumors, indicating that tumor suppressor genes reside at these loci. In this study, we have examined the properties of the Wnt signaling antagonist secreted frizzled-related protein (sFRP) 1 as a candidate for this role at c8p11.2. An initial survey of 10 colorectal tumors, selected by the presence of isolated short deletions of the 8p11.2 region, identified three chain-terminating mutations, all within the first exon, which encodes the cysteine-rich domain. None of these tumors exhibited microsatellite instability, indicating intact mismatch repair gene function. The preserved sFRP1 alleles in the remaining seven tumors each contained a polymorphic three-base insertion in the signal sequence, but in a broader study, no association was found between this and the development of colorectal cancer. Epigenetic inhibition of sFRP1 transcription was investigated, and increased methylation of the promotor region was demonstrated in an additional cohort of 51 locally advanced colorectal cancers. Hypermethylation was identified in 40 of 49 (82%) cancers and in only 11 of 36 (30%) matched normal mucosal samples (P < 0.001). Semiquantitative analysis, by real-time PCR, of mRNA expression in 37 of the same cohort of 51 cancers revealed that sFRP1 mRNA expression was down-regulated in 28 (76%) cases compared with matched normal large bowel mucosa. The 3 end of the sFRP1 mRNA also was found to be alternatively spliced, compared with the prototype liver and lung forms, in the colon and a number of other tissues, yielding an extended COOH terminus, which may influence its activity in a tissue-specific manner. The inactivation and down-regulation of sFRP1 observed are consistent with it acting as a tumor suppressor gene in colorectal carcinogenesis. Because ␤-catenin is constitutively active in the majority of colorectal tumors, it is unlikely that sFRP1 can act in the canonical Wnt response pathway. Therefore, we propose that the reduced activity or absence of sFRP1 allows the transduction of noncanonical Wnt signals, which contribute to tumor progression.

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Roles for neuregulins in human cancer

Stove

Bracke

2005

Clin Exp Metastasis

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The human epidermal growth factor (EGF) receptor (HER) family of receptor tyrosine kinases has frequently been implicated in cancer. Apart from overexpression or mutation of these receptors, also the aberrant autocrine or paracrine activation of HERs by EGF-like ligands may be important in cancer progression. Neuregulins constitute a family of EGF-like ligands that bind to HER3 or HER4, preferably forming heterodimers with the orphan receptor HER2. Mesenchymal neuregulin typically serves as a pro-survival and pro-differentiation signal for adjacent epithelia. Disruption of the balance between proliferation and differentiation, because of autocrine production by the epithelial cells, increased sensitivity to paracrine signals or disruption of the spatial organization, may lead to constitutive receptor activation, in the absence of receptor overexpression. Consequently, the analysis of ligand expression and/or activated receptors in tumor samples may broaden the group of patients that can benefit from targeted therapies.

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Loss of heterozygosity at microsatellite markers from region p11-21 of chromosome 8 in microdissected breast tumor but not in peritumoral cells

Cited by 9 publications

References 0 publications

High‐resolution analysis of genomic alteration on chromosome arm 8p in urothelial carcinoma

High‐resolution analysis of genomic alteration on chromosome arm 8p in urothelial carcinoma

The Wnt Antagonist sFRP1 in Colorectal Tumorigenesis

Roles for neuregulins in human cancer

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