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Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Kai Wang

PROVIDER: E-GEOD-38326 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma.

Wang Kai K Lim Ho Yeong HY Shi Stephanie S Lee Jeeyun J Deng Shibing S Xie Tao T Zhu Zhou Z Wang Yuli Y Pocalyko David D Yang Wei Jennifer WJ Rejto Paul A PA Mao Mao M Park Cheol-Keun CK Xu Jiangchun J

Hepatology (Baltimore, Md.) 20130701 2

<h4>Unlabelled</h4>Cancer is a genetic disease with frequent somatic DNA alterations. Studying recurrent copy number aberrations (CNAs) in human cancers would enable the elucidation of disease mechanisms and the prioritization of candidate oncogenic drivers with causal roles in oncogenesis. We have comprehensively and systematically characterized CNAs and the accompanying gene expression changes in tumors and matched nontumor liver tissues from 286 hepatocellular carcinoma (HCC) patients. Our an ...[more]

PMID: 23505090

Similar Datasets

Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma [cell line]

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

Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma [tumor]

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

The pattern of genomic instability during bladder cancer progression (part 1)

Project description:The Illumina SNP bead arrays were done for two metachronous tumors and the blood from a given patient. It was used to define copy number abnormalities in order to support subclonal population analysis in this patient. Three samples were analysed concerning two metachronous tumor samples and a blood sample from the same patient.

2014-07-01 | E-GEOD-50666 | biostudies-arrayexpress

Homozygosity mapping in a consanguineous family with osteogenesis imperfecta (OI)

Project description:Homozygosity mapping using genome-wide SNP arrys is a useful tool to map causative genes of mendelian disorders in consanguineous patients To search for LOH (loss of heterozygosity) regions we hybridized genomic DNA from a OI patient and a normal sibling against Human610quad beadarrays from Illumina (www.illumina.com). Genotyping data was analyzed with BeadStudio software (www.illumina.com) Genomic DNAs from OI affected individual and non-affected sibling were hybridized each on an Illumina Human610Quad Genotyping BeadChip. Image data was analyzed using Beadstudio 3.1.3 software. CNV and LOH (larger than 1 Mb) analysis was performed using the cnvPartition 2.3.4. It was considered as a region of interest those showing LOH in the affected individual but not in the non-affected sibling.

2010-11-01 | E-GEOD-21958 | biostudies-arrayexpress

Concomitant deletions of tumor suppressor genes MEN1 and AIP are essential for the pathogenesis of the brown fat tumor hibernoma

Project description:Hibernomas are benign tumors with morphological features resembling brown fat. They consistently display cytogenetic rearrangements, typically translocations, involving chromosome band 11q13. Here we demonstrate that these aberrations are associated with concomitant deletions of AIP and MEN1, tumor suppressor genes that are located 3 Mb apart and that underlie the hereditary syndromes pituitary adenoma predisposition and multiple endocrine neoplasia type I. MEN1 and AIP displayed a low expression in hibernomas whereas the expression of genes up-regulated in brown fat-PPARA, PPARG, PPARGC1A, and UCP1-was high. Thus, loss of MEN1 and AIP is likely to be pathogenetically essential for hibernoma development. Simultaneous loss of two tumor suppressor genes has not previously been shown to result from a neoplasia-associated translocation. Furthermore, in contrast to the prevailing assumption that benign tumors harbor relatively few genetic aberrations, the present analyses demonstrate that a considerable number of chromosome breaks are involved in the pathogenesis of hibernoma. Global copy number analysis was performed using single nucleotide polymorphism (SNP) array. Cases 1-14 were hybridized onto Illumina Human1M-Duo v3.0 (and Human CNV370-Quad v3.0) BeadChip (Illumina, San Diego, CA, USA), following standard protocols supplied by the manufacturer. Case 15 was analyzed using Illumina Human Omni-Quad BeadChip. Normal blood DNA was analyzed in cases 1, 2, 4 and 6 using the Human CNV370-Quad v3.0 BeadChip. Data analysis was done using the BeadStudio software (Illumina).

2010-11-24 | E-GEOD-19040 | biostudies-arrayexpress

Genomic aberrations predicts survival in clear cell renal cell carcinoma

Project description:Detailed genetic profiling of clear cell Renal Cell Carcinoma (ccRCC) has shown that these tumors are characterized by large genetic heterogeneity with some genomic regions commonly affected by structural changes. Loss on chromosomes 3p and 14q, and gain on 5q and 7 are examples of alterations commonly reported in ccRCC. However, there is no consensus regarding the potential prognostic information carried by the identified alterations. We report on poorer outcome for patients with gain on 5q and 7, and loss on 9p, 9q and 14q. These aberrations were in addition found more frequently in metastasized tumors, suggesting that they are markers for advanced disease. Furthermore, the presence of M-bM-^IM-% 4 common aberrations was associated with decreased survival time. Shorter relative telomere length (RTL) has been associated with loss of chromosomal regions in ccRCC tumors, but we found no significant associations between tumor RTL and chromosomal deletions. However, significantly lower tumor-to-nontumor (T/N) RTL ratio was detected for patients with loss on 4q and 9p. Finally, we found a minimum region (MR) of genetic loss of 1.4 Mbp on chromosome 9p and this region contains only one gene, the tumor suppressor candidate 1 gene (TUSC1). TUSC1 has been implicated in lung carcinogenesis and our result further strengthens its role in tumorigenesis. Seventy-four ccRCC tumors and 22 paired normal kidney cortex and blood samples were genotyped on Illuminas HumanCytoSNP-12 bead chips.

2014-07-01 | E-GEOD-30460 | biostudies-arrayexpress

The pattern of genomic instability during bladder cancer progression

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-07-01 | E-GEOD-50668 | biostudies-arrayexpress

High concordance between SNPs identified by the porcine 60K BeadChip genotyping array (Illumina) and the assembly-versus-assembly method

Project description:Porcine 60K BeadChip genotyping arrays (Illumina) are increasingly being applied in pig genomics to validate SNPs identified by re-sequencing or assembly-versus-assembly method. Here we report that more than 98% SNPs identified from the porcine 60K BeadChip genotyping array (Illumina) were consistent with the SNPs identified from the assembly-based method. This result demonstrates that whole-genome de novo assembly is a reliable approach to deriving accurate maps of SNPs. To compare SNPs identified by genotyping arrays and de novo assembly method, we genotyped 10 pig breeds by porcine 60K BeadChip genotyping array (Illumina), including 1 berkshire pig, 1 hampshire pig, 1 landrace pig, 1 large white pig,1 piÃ©train pig, 1 bamei pig,1 jinhua pig, 1 meishan pig, 1 rongchang pig and 1 Tibetan wild boar.

2016-07-05 | E-GEOD-83910 | biostudies-arrayexpress

A genomewide association study for bronchopulmonary dysplasia using DNA pooling

Project description:Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in premature infants. Recent studies have highlighted the contribution of genetic factors to BPD susceptibility. Our aim was to identify the genetic variants associated to BPD, through a genomewide association study. Two discovery series were performed, using a DNA pooling-based strategy in Caucasian and black African neonates. DNA pooling studies were performed in two discovery series. The first discovery series was made up of 22 Caucasian infants with BPD and 76 Caucasian controls. The second discovery series was composed of 21 black African infants with BPD and 86 black African controls. Equimolar amounts of each DNA sample were then added to either the case or control pool, for each series. To control for experimental errors, several independent sets of pools were constructed. Concerning the Caucasian series, 3 sets of identical pools were constructed with one made in double quantity in order to hybridize it twice, which led to 4 independent replicates. Concerning the black African series, 4 sets of identical pools were constructed and each was hybridized once, leading also to 4 independent replicates. Genotyping was performed using the Infinium II Illumina HumanHap300 Genotyping BeadChip array for the Caucasian population and the Illumina HumanHap650Y array for the black African population. Each replicate was hybridized once which led to 4 arrays for each case and control pools and for each population. A total of 16 arrays were performed. technical replicate: Sample 1, Sample 2, Sample 3, Sample 4 technical replicate: Sample 5, Sample 6, Sample 7, Sample 8 technical replicate: Sample 9, Sample 10, Sample 11, Sample 12 technical replicate: Sample 13, Sample 14, Sample 15, Sample 16

2011-11-22 | E-GEOD-22284 | biostudies-arrayexpress

SNP genotyping analyses for the Chinese indigenous pig breeds and commercial pig breeds

Project description:Genome-wide SNP genotyping array can genotyped SNP highthroughly. It can be used in many aspects, such as phylogeny relationships, genome-wide association studies, copy number identification. 9 Chinese indigenous pig, 4 commercial pigs and 1 wild pig were genotyped by PorcineSNP60 array (Illumina) for exploring the phylogeny relationships among them.

2013-05-09 | E-GEOD-46733 | biostudies-arrayexpress

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