Across-species comprehensive copy number analyses identifies subtype-specific drivers of breast cancer development
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PROVIDER: PRJNA227098 | ENA |
REPOSITORIES: ENA
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Project description:A large number of DNA copy number alterations (CNAs) exist in human breast cancers, and thus characterizing the most frequent ones is key to advancing therapeutics because it is likely that these recurrent CNAs contain breast tumor ‘drivers’ (i.e. causal genes). Here, we have comprehensively profiled a large set of human breast tumors and mouse models of mammary cancers using DNA copy number and gene expression microarrays. By using an across species genetic conservation approach, we identified common altered regions/genes that were similarly altered in both human and mouse breast tumors; additionally, we further demonstrate that many of these conserved CNA regions are also expression-subtype specific, such as the common gain of 1q21-23, or loss of 5q in mouse and human Basal-like cancers. Published functional studies further validated likely driver genes from these regions including Nicastrin (NCSTN) on 1q23 in Basal-like breast cancers. The ability to integrate copy number, and expression data, from mouse and human breast tumors identified at least 25 regions of shared subtype specific alternations, which has identified a number of known drivers and a few regions that merit additional studies.
2014-12-31 | GSE52173 | GEO
Project description:Cancer is a genetic disease with frequent somatic alterations in DNA. Study of recurrent copy number aberrations (CNAs) in human cancers would enable the elucidation of disease mechanisms and the identification of key oncogenic drivers with causal roles in oncogenesis. We have comprehensively and systematically characterized CNAs and accompanied gene expression changes in the tumors and their matched non-tumor liver tissues from 286 hepatocellular carcinoma (HCC) patients. Our analysis identified 29 recurrently amplified regions and 22 deleted regions with a high level of copy number changes, harboring established oncogenes and tumor suppressors, including CCND1, MET, CDKN2A and CDKN2B, as well as many other genes not previously reported to be involved in liver carcinogenesis. Cis-acting genes in the amplification and deletion peaks were enriched in core cancer pathways, including cell cycle, p53, PI3K, MAPK, Wnt and TGFβ signaling in large proportions of HCCs. We further validated two candidate driver genes, BCL9 and MTDH, from the recurrent focal amplification peaks and showed that they play a significant role in HCC growth and survival. In summary, we have demonstrated that characterizing the CNA landscape in HCC will facilitate the understanding of disease mechanisms and the identification of oncogenic drivers that may serve as potential therapeutic targets for the treatment of this devastating disease. Two hundred and eighty-six hepatocellular carcinoma tumors and their matched non-tumor adjacent liver tissue samples were genotyped using Illumina HumanOmni1-Quad BeadChip to estimate their somatic copy number profiles.
2013-05-22 | E-GEOD-38323 | biostudies-arrayexpress
Project description:Great Ape Copy Number Variation
| PRJNA144461 | ENA
Project description:Cancer is a genetic disease with frequent somatic alterations in DNA. Study of recurrent copy number aberrations (CNAs) in human cancers would enable the elucidation of disease mechanisms and the identification of key oncogenic drivers with causal roles in oncogenesis. We have comprehensively and systematically characterized CNAs and accompanied gene expression changes in the tumors and their matched non-tumor liver tissues from 286 hepatocellular carcinoma (HCC) patients. Our analysis identified 29 recurrently amplified regions and 22 deleted regions with a high level of copy number changes, harboring established oncogenes and tumor suppressors, including CCND1, MET, CDKN2A and CDKN2B, as well as many other genes not previously reported to be involved in liver carcinogenesis. Cis-acting genes in the amplification and deletion peaks were enriched in core cancer pathways, including cell cycle, p53, PI3K, MAPK, Wnt and TGFβ signaling in large proportions of HCCs. We further validated two candidate driver genes, BCL9 and MTDH, from the recurrent focal amplification peaks and showed that they play a significant role in HCC growth and survival. In summary, we have demonstrated that characterizing the CNA landscape in HCC will facilitate the understanding of disease mechanisms and the identification of oncogenic drivers that may serve as potential therapeutic targets for the treatment of this devastating disease. Thirty hepatocellular carcinoma cell lines were genotyped using Illumina HumanOmni1-Quad BeadChip to estimate their copy number profiles relative to pooled Hapmap samples.
2013-05-22 | E-GEOD-38207 | biostudies-arrayexpress
Project description:We performed copy number analysis of high-grade osteosarcoma samples. in order to detect osteosarcoma drivers, we integrated these data with genome-wide gene expression data. We performed two different methods - a non-paired and a paired integrative analysis.
2012-03-28 | GSE33153 | GEO
Project description:Cancer is a genetic disease with frequent somatic alterations in DNA. Study of recurrent copy number aberrations (CNAs) in human cancers would enable the elucidation of disease mechanisms and the identification of key oncogenic drivers with causal roles in oncogenesis. We have comprehensively and systematically characterized CNAs and accompanied gene expression changes in the tumors and their matched non-tumor liver tissues from 286 hepatocellular carcinoma (HCC) patients. Our analysis identified 29 recurrently amplified regions and 22 deleted regions with a high level of copy number changes, harboring established oncogenes and tumor suppressors, including CCND1, MET, CDKN2A and CDKN2B, as well as many other genes not previously reported to be involved in liver carcinogenesis. Cis-acting genes in the amplification and deletion peaks were enriched in core cancer pathways, including cell cycle, p53, PI3K, MAPK, Wnt and TGFβ signaling in large proportions of HCCs. We further validated two candidate driver genes, BCL9 and MTDH, from the recurrent focal amplification peaks and showed that they play a significant role in HCC growth and survival. In summary, we have demonstrated that characterizing the CNA landscape in HCC will facilitate the understanding of disease mechanisms and the identification of oncogenic drivers that may serve as potential therapeutic targets for the treatment of this devastating disease.
2013-05-22 | GSE38323 | GEO
Project description:Evolution of transposable element copy number control in yeast
| PRJEB33725 | ENA
Project description:We performed copy number analysis of high-grade osteosarcoma samples. in order to detect osteosarcoma drivers, we integrated these data with genome-wide gene expression data. We performed two different methods - a non-paired and a paired integrative analysis. Copy number analysis was performed on 32 pre-treatment high-grade osteosarcoma diagnostic biopsies, of which 29 overlapped with the 84 samples used for gene expression analyses.
2012-03-27 | E-GEOD-33153 | biostudies-arrayexpress
Project description:Cancer is a genetic disease with frequent somatic alterations in DNA. Study of recurrent copy number aberrations (CNAs) in human cancers would enable the elucidation of disease mechanisms and the identification of key oncogenic drivers with causal roles in oncogenesis. We have comprehensively and systematically characterized CNAs and accompanied gene expression changes in the tumors and their matched non-tumor liver tissues from 286 hepatocellular carcinoma (HCC) patients. Our analysis identified 29 recurrently amplified regions and 22 deleted regions with a high level of copy number changes, harboring established oncogenes and tumor suppressors, including CCND1, MET, CDKN2A and CDKN2B, as well as many other genes not previously reported to be involved in liver carcinogenesis. Cis-acting genes in the amplification and deletion peaks were enriched in core cancer pathways, including cell cycle, p53, PI3K, MAPK, Wnt and TGFβ signaling in large proportions of HCCs. We further validated two candidate driver genes, BCL9 and MTDH, from the recurrent focal amplification peaks and showed that they play a significant role in HCC growth and survival. In summary, we have demonstrated that characterizing the CNA landscape in HCC will facilitate the understanding of disease mechanisms and the identification of oncogenic drivers that may serve as potential therapeutic targets for the treatment of this devastating disease.
2013-05-22 | GSE38207 | GEO
Project description:Copy Number Variations in Genomic Disorders
| PRJNA75521 | ENA