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High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.

Bekhouche I, Finetti P, Adelaïde J, Ferrari A, Tarpin C, Charafe-Jauffret E, Charpin C, Houvenaeghel G, Jacquemier J, Bidaut G, Birnbaum D, Viens P, Chaffanet M, Bertucci F - PLoS ONE (2011)

Bottom Line: We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration.Our results suggest a higher genomic instability of IBC.

View Article: PubMed Central - PubMed

Affiliation: Marseille Cancer Research Center (CRCM), UMR891 Inserm, Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France.

ABSTRACT

Background: Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.

Methodology/findings: Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration.

Conclusions: Our results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets.

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Related in: MedlinePlus

Chromosomal location of the IBC candidate oncogenes.The 24 candidate oncogenes defined by comparative integrated analysis are shown associated with their corresponding chromosome CNA frequency plot in 49 IBCs and 124 nIBCs. A threshold value of log2 ratio >/0.5/ was used to draw chromosome CNA frequency plots using CGH Analytics® software.
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pone-0016950-g002: Chromosomal location of the IBC candidate oncogenes.The 24 candidate oncogenes defined by comparative integrated analysis are shown associated with their corresponding chromosome CNA frequency plot in 49 IBCs and 124 nIBCs. A threshold value of log2 ratio >/0.5/ was used to draw chromosome CNA frequency plots using CGH Analytics® software.

Mentions: Out of the 628 genes identified by supervised analysis with CNA frequencies different between IBCs and nIBCs, 500 were present on the Affymetrix microarrays. They were represented by 748 probe sets on these microarrays, and 4,259 probes on the Agilent microarrays. From these 500 genes, we identified 24 genes whose expression was deregulated in relation to CNA with significant differences between IBCs and nIBCs (Table 3; Table S9; Figure 2). In all cases, the transcriptional deregulation was associated with IBCs only and corresponded to an overexpression related to a gain (21 genes) and/or amplification (13 genes). By definition, these 24 genes were also overexpressed in IBCs as compared to nIBCs. Twenty of these genes are located in 8q22–q24 and 17q21, including PAPBC1, RAD21, ATAD2, MTSS1, SQLE, ST3GAL1, C17orf37, ABCC3 and PTPN2, previously reported as cancer-related genes. In contrast, no candidate gene was both downregulated and loss-targeted in IBCs.


High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.

Bekhouche I, Finetti P, Adelaïde J, Ferrari A, Tarpin C, Charafe-Jauffret E, Charpin C, Houvenaeghel G, Jacquemier J, Bidaut G, Birnbaum D, Viens P, Chaffanet M, Bertucci F - PLoS ONE (2011)

Chromosomal location of the IBC candidate oncogenes.The 24 candidate oncogenes defined by comparative integrated analysis are shown associated with their corresponding chromosome CNA frequency plot in 49 IBCs and 124 nIBCs. A threshold value of log2 ratio >/0.5/ was used to draw chromosome CNA frequency plots using CGH Analytics® software.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037286&req=5

pone-0016950-g002: Chromosomal location of the IBC candidate oncogenes.The 24 candidate oncogenes defined by comparative integrated analysis are shown associated with their corresponding chromosome CNA frequency plot in 49 IBCs and 124 nIBCs. A threshold value of log2 ratio >/0.5/ was used to draw chromosome CNA frequency plots using CGH Analytics® software.
Mentions: Out of the 628 genes identified by supervised analysis with CNA frequencies different between IBCs and nIBCs, 500 were present on the Affymetrix microarrays. They were represented by 748 probe sets on these microarrays, and 4,259 probes on the Agilent microarrays. From these 500 genes, we identified 24 genes whose expression was deregulated in relation to CNA with significant differences between IBCs and nIBCs (Table 3; Table S9; Figure 2). In all cases, the transcriptional deregulation was associated with IBCs only and corresponded to an overexpression related to a gain (21 genes) and/or amplification (13 genes). By definition, these 24 genes were also overexpressed in IBCs as compared to nIBCs. Twenty of these genes are located in 8q22–q24 and 17q21, including PAPBC1, RAD21, ATAD2, MTSS1, SQLE, ST3GAL1, C17orf37, ABCC3 and PTPN2, previously reported as cancer-related genes. In contrast, no candidate gene was both downregulated and loss-targeted in IBCs.

Bottom Line: We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration.Our results suggest a higher genomic instability of IBC.

View Article: PubMed Central - PubMed

Affiliation: Marseille Cancer Research Center (CRCM), UMR891 Inserm, Institut Paoli-Calmettes, Department of Molecular Oncology, Marseille, France.

ABSTRACT

Background: Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.

Methodology/findings: Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration.

Conclusions: Our results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets.

Show MeSH
Related in: MedlinePlus