Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA167716 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma [cell line]
| PRJNA167447 | 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. 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: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: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: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:Hepatocellular carcinoma tumor samples were profiled for chromsomal copy number changes on Affymterix 100K SNP arrays Analysis of copy number changes in Hepatocellular Carcinoma
2012-01-19 | E-GEOD-34957 | biostudies-arrayexpress
Project description:Chromosomal DNA copy number alterations are a hallmark of human malignancies, including hepatocellular carcinoma (HCC). However, which oncogenes or tumor suppressors located on regions with DNA copy number aberration may contribute to HCC initiation and progression still remain obscure. Here we performed a genome-wide DNA copy number analysis on human HCC samples to identify novel potential oncogenes or tumor suppressors with DNA copy number aberrations. Genome-wide DNA copy numbers analysis was performed with single nucleotide polymorphism micoarray. RT-PCR and immunohistochemical staining were employed to evaluate the NOXIN expression in HCC samples. Colony formation, cell cycle analysis and tumor xenograft assays were performed to assess the role of NOXIN in HCC cells. Reciprocal co-immunoprecipitation experiments were used to detect the interaction between NOXIN and DNA polymerase a primase. Genome-wide DNA copy number analysis on 43 paired HCC samples indentified the smallest DNA amplification region containing NOXIN, along with the elevated transcript. NOXIN overexpression was significantly associated with HCC tumor stage. Enforced NOXIN promoted cellular proliferation, colony formation, cell migration and in vivo tumorigenicity, whereas RNA interference against NOXIN can attenuate these effects. Interestingly, NOXIN overexpression can accelerate the G1-S transition of cell cycle progression through enhancing DNA synthesis in HCC cells, as indicated by bromodeoxyuridine incorporation. Furthermore, NOXIN can interact with DNA polymerase a, implying that NOXIN may promote de novo DNA synthesis via affiliating formation of DNA polymerase-primase complex. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from hepatocellular carcinoma and adjacent liver tissue samples. Copy number analysis of Affymetrix 500K SNP arrays was performed for 43 hepatocellular carcinoma tissue samples, which their adjacent liver tissues were used as references for copy number inference.
2013-07-30 | E-GEOD-49317 | biostudies-arrayexpress
Project description:Ovarian cancer is characterized by multiple structural aberrations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and till date, the histotype-specific copy number landscape has been difficult to elucidate. To dissect the heterogeneity of ovarian cancer and understand the pathogenesis of its various histotypes, we developed an in silico hypothesis-driven workflow to identify histotype-specific copy number aberrations across multiple datasets of epithelial ovarian cancer. In concordance with previous studies on global copy number changes, our study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here a comprehensive histotype-specific copy number landscape of ovarian cancer and showed that there is genomic diversity between the histotypes; some involving well known cancer genes and some novel potential driver genes. Besides preferential occurrence of alterations in some histotypes, opposite trends of alteration were observed; such as ERBB2 amplification in mucinous but deletion in serous tumors. The landscape highlights the need for identifying histotype-specific aberrations in ovarian cancer and present potential to tailor management of ovarian cancer based on molecular signature of histotypes. 56 samples containing the 4 histotypes were used for this study. It contained 12 clear cell carcinoma, 6 endometrioid adenocarcinoma, 2 mucinous adenocarcinoma, 5 mucinous-borderline tumors, 26 serous adenocarcinoma, and 5 serous-borderline tumors.
2012-10-25 | E-GEOD-30274 | biostudies-arrayexpress
Project description:Ovarian cancer is characterized by multiple structural aberrations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and till date, the histotype-specific copy number landscape has been difficult to elucidate. To dissect the heterogeneity of ovarian cancer and understand the pathogenesis of its various histotypes, we developed an in silico hypothesis-driven workflow to identify histotype-specific copy number aberrations across multiple datasets of epithelial ovarian cancer. In concordance with previous studies on global copy number changes, our study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here a comprehensive histotype-specific copy number landscape of ovarian cancer and showed that there is genomic diversity between the histotypes; some involving well known cancer genes and some novel potential driver genes. Besides preferential occurrence of alterations in some histotypes, opposite trends of alteration were observed; such as ERBB2 amplification in mucinous but deletion in serous tumors. The landscape highlights the need for identifying histotype-specific aberrations in ovarian cancer and present potential to tailor management of ovarian cancer based on molecular signature of histotypes. 56 samples containing the 4 histotypes were used for this study. It contained 12 clear cell carcinoma, 6 endometrioid adenocarcinoma, 2 mucinous adenocarcinoma, 5 mucinous-borderline tumors, 26 serous adenocarcinoma, and 5 serous-borderline tumors. Data was pre-processed and normalized with Hapmap JPT using the Affymetric Genotyping Console.
2012-10-25 | E-GEOD-30283 | biostudies-arrayexpress