Genomic and Expression Profiling of Chromosome 17 in Breast Cancer Reveals Complex Patterns of Alterations and Novel Candidate Genes

Orsetti, Béatrice; Nugoli, Mélanie; Cervera, Nathalie; Lasorsa, Laurence; Chuchana, Paul; Ursule, Lisa; Nguyen, Catherine; Redon, Richard; Manoir, Stanislas du; Rodrı́guez, Carmen; Theillet, Charles

doi:10.1158/0008-5472.can-04-0756

Cited by 84 publications

(93 citation statements)

References 22 publications

(22 reference statements)

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“…Most importantly, this approach circumvents limitations of previous analysis, as it takes into account (1) the possible existence of multiple cores in a single amplicon and (2) the hypothesis that each amplicon contains more than one amplicon driver. It should be noted, however, that STARD3 and GRB7, two of the most commonly overexpressed genes in the HER2 amplicon (17q12-q21) in previous studies [4,44], failed to display a significant correlation between amplification and overexpression, owing to the suboptimal performance of the respective cDNA probes. Similar analyses were performed for other recurrent amplicons in these cell lines and genes that may be considered as potential amplicon drivers for each amplicon are described in Supplementary Table S6.…”

Section: Identification Of Likeliest Amplicon Drivers Of Recurrent Ammentioning

confidence: 83%

A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines

Mackay

Tamber

Fenwick

et al. 2009

Breast Cancer Res Treat

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Section: Identification Of Likeliest Amplicon Drivers Of Recurrent Ammentioning

confidence: 83%

A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines

Mackay

Tamber

Fenwick

et al. 2009

Breast Cancer Res Treat

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“…Inversions are difficult to detect but are an attractive explanation for the amplification of apparently distinct regions of one chromosome (e.g. Orsetti et al, 2004): inversion, creating an oncogenic junction, would be followed by amplification of one inversion junction, manifest as two apparent regions of amplification by array CGH, in the same way as amplifications on distinct chromosomes can be coamplifications (Guan et al, 1994;Bautista and Theillet, 1998;Volik et al, 2003).…”

Section: Inversionsmentioning

confidence: 99%

High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation

et al. 2006

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The short arm of chromosome 8, 8p, is often rearranged in carcinomas, typically showing distal loss by unbalanced translocation. We analysed 8p rearrangements in 48 breast, pancreatic and colon cancer cell lines by fluorescence in situ hybridization (FISH) and array comparative genomic hybridization, with a tiling path of 0.2 Mb resolution over 8p12 and 1 Mb resolution over chromosome 8. Selected breast lines (MDA-MB-134, MDA-MB-175, MDA-MB-361, T-47D and ZR-75-1) were analysed further. Most cell lines showed loss of 8p distal to a break that was between 31 Mb (5 0 to NRG1) and the centromere, but the translocations were accompanied by variable amplifications, deletions and inversions proximal to this break. The 8p12 translocation in T-47D was flanked by an inversion of 4 Mb, with a 100 kb deletion at the proximal end. The dicentric t(8;11) in ZR-75-1 carries multiple rearrangements including interstitial deletions, a triplicated translocation junction between NRG1 and a fragment of 11q (unconnected to CCND1), and two separate amplifications, of FGFR1 and CCND1 . We conclude that if there is a tumour suppressor gene on 8p it may be near 31 Mb, for example WRN; but the complexity of 8p rearrangements suggests that they target various genes proximal to 31 Mb including NRG1 and the amplicon centred around ZNF703/FLJ14299.

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“…Coverage of chromosomes 8 and 17 has been described by Orsetti et al (2004) and Gelsi-Boyer et al (2005). Chromosome 1 was covered by 257 BAC clones selected as follows: 225 BAC clones from the Barbara Trask collection (CHORI) http://www.ncbi.nlm.…”

Section: Genomic Arraysmentioning

confidence: 99%

“…Probe DNA to be spotted was prepared by DOP-PCR amplification on 10 ng of BAC matrix DNA in a final reaction volume of 100 ml. Primer sequences and DOP-PCR protocol used are available on the Sanger Center web site (http://www.sanger.ac.uk/HGP/methods/cytogenetics/ DOPPCR.shtml) (Orsetti et al, 2004). We performed this with slight modifications: the second round DOP-PCR primer was not aminolinked.…”

Section: Genomic Arraysmentioning

confidence: 99%

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

et al. 2006

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Chromosome 1 is involved in quantitative anomalies in 50 -60% of breast tumours. However, the structure of these anomalies and the identity of the affected genes remain to be determined. To characterise these anomalies and define their consequences on gene expression, we undertook a study combining array-CGH analysis and expression profiling using specialised arrays. Array-CGH data showed that 1p was predominantly involved in losses and 1q almost exclusively in gains. Noticeably, high magnitude amplification was infrequent. In an attempt to fine map regions of copy number changes, we defined 19 shortest regions of overlap (SROs) for gains (one at 1p and 18 at 1q) and of 20 SROs for losses (all at 1p). These SROs, whose sizes ranged from 170 kb to 3.2 Mb, represented the smallest genomic intervals possible based on the resolution of our array. The elevated incidence of gains at 1q, added to the wellestablished concordance between DNA copy increase and augmented RNA expression, made us focus on gene expression changes at this chromosomal arm. To identify candidate oncogenes, we studied the RNA expression profiles of 307 genes located at 1q using a home-made built cDNA array. We identified 30 candidate genes showing significant overexpression correlated to copy number increase. In order to substantiate their involvement, RNA expression levels of these candidate genes were measured by quantitative (Q)-RT -PCR in a panel of 25 breast cancer cell lines previously typed by array-CGH. Q -PCR showed that 11 genes were significantly overexpressed in the presence of a genomic gain in these cell lines, and 20 overexpressed when compared to normal breast.

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Genomic and Expression Profiling of Chromosome 17 in Breast Cancer Reveals Complex Patterns of Alterations and Novel Candidate Genes

Cited by 84 publications

References 22 publications

A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines

A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines

High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation

Genetic profiling of chromosome 1 in breast cancer: mapping of regions of gains and losses and identification of candidate genes on 1q

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