Transcription profiling, comparative genomic hybridization, genotyping and methylation profiling by array of human breast cancer cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Grigoriadis Anita
PROVIDER: S-ECPF-TABM-928 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Integrative analysis of breast cancer cell lines, using expression, comparative genomics, SNP and methylation profiling
2012-11-09 | E-TABM-928 | biostudies-arrayexpress
Project description:Breast cancer is a profoundly heterogeneous disease with respect to biological and clinical behavior. Gene expression profiling has been used to dissect this complexity and stratify tumors into intrinsic gene expression subtypes associated with distinct biology, patient outcome and different genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes. We applied global DNA copy number and gene expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy number aberrations and genomic subgroups of breast cancer. We identified 31 genomic regions that were highly amplified in >1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions (66 and 67 with DNA copy number gain and loss, respectively) revealed six genomic subtypes, termed: 17q12, basal-complex, luminal-simple, luminal-complex, amplifier and mixed subtype. Four of them had striking similarity to intrinsic gene expression subtypes and showed association to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having better prognosis while the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene expression subtypes, the former being enriched for 8p12-amplified cases while the mixed subtype included many tumors with predominantly DNA copy number losses and poor prognosis. Genomic profiling of 359 breast tumors using tiling BAC aCGH. A number of cases were hybridized as replicates or replicate as dye-swaps. Gene expression profiling of 359 breast tumors using 55K oligonucleotide microarrays.
| S-ECPF-GEOD-22133 | biostudies-other
Project description:Genomic copy number aberrations (CNAs) in gastric cancer have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis. However, involvement of genomic CNAs in the process of submucosal invasion and lymph node metastasis in early gastric cancer is still poorly understood. In this study, to address this issue, we collected a total of 59 tumor samples from 27 patients with submucosal-invasive gastric cancers (SMGC), analyzed their genomic profiles by array CGH, and compared them between paired samples of mucosal (MU) and submucosal (SM) invasion (23 pairs), and SM invasion and lymph node (LN) metastasis (9 pairs). Initially, we hypothesized that acquisition of specific CNA(s) is important for these processes. However, we observed no significant difference in the number of genomic CNAs between paired MU and SM, and between paired SM and LN. Furthermore, we were unable to find any CNAs specifically associated with SM invasion or LN metastasis. Among the 23 cases analyzed, 15 had some similar pattern of genomic profiling between SM and MU. Interestingly, 13 of the 15 cases also showed some differences in genomic profiles. These results suggest that the majority of SMGCs are composed of heterogeneous subpopulations derived from the same clonal origin. Comparison of genomic CNAs between SMGCs with and without LN metastasis revealed that gain of 11q13, 11q14, 11q22, 14q32 and amplification of 17q21 were more frequent in metastatic SMGCs, suggesting that these CNAs are related to LN metastasis of early gastric cancer. In conclusion, our data suggest that generation of genetically distinct subclones, rather than acquisition of specific CNA at MU, is integral to the process of submucosal invasion, and that subclones that acquire gain of 11q13, 11q14, 11q22, 14q32 or amplification of 17q21 are likely to become metastatic.
| S-EPMC3141024 | biostudies-literature
Project description:We designed a study to investigate genetic relationships between primary tumors of oral squamous cell carcinoma (OSCC) and their lymph node metastases, and to identify genomic copy number aberrations (CNAs) related to lymph node metastasis. For this purpose, we collected a total of 42 tumor samples from 25 patients and analyzed their genomic profiles by array-based comparative genomic hybridization. We then compared the genetic profiles of metastatic primary tumors (MPTs) with their paired lymph node metastases (LNMs), and also those of LNMs with non-metastatic primary tumors (NMPTs). Firstly, we found that although there were some distinctive differences in the patterns of genomic profiles between MPTs and their paired LNMs, the paired samples shared similar genomic aberration patterns in each case. Unsupervised hierarchical clustering analysis grouped together 12 of the 15 MPT-LNM pairs. Furthermore, similarity scores between paired samples were significantly higher than those between non-paired samples. These results suggested that MPTs and their paired LNMs are composed predominantly of genetically clonal tumor cells, while minor populations with different CNAs may also exist in metastatic OSCCs. Secondly, to identify CNAs related to lymph node metastasis, we compared CNAs between grouped samples of MPTs and LNMs, but were unable to find any CNAs that were more common in LNMs. Finally, we hypothesized that subpopulations carrying metastasis-related CNAs might be present in both the MPT and LNM. Accordingly, we compared CNAs between NMPTs and LNMs, and found that gains of 7p, 8q and 17q were more common in the latter than in the former, suggesting that these CNAs may be involved in lymph node metastasis of OSCC. In conclusion, our data suggest that in OSCCs showing metastasis, the primary and metastatic tumors share similar genomic profiles, and that cells in the primary tumor may tend to metastasize after acquiring metastasis-associated CNAs.
| S-EPMC3573022 | biostudies-literature
Project description:BackgroundRectal cancer is one of the most common cancers in the world. Early detection and early therapy are important for the control of death caused by rectal cancer. The present study aims to investigate the genomic alterations in rectal adenoma and carcinoma.MethodsWe detected the genomic changes of 8 rectal adenomas and 8 carcinomas using array CGH. Then 14 genes were selected for analyzing the expression between rectal tumor and paracancerous normal tissues as well as from adenoma to carcinoma by real-time PCR. The expression of GPNMB and DIS3 were further investigated in rectal adenoma and carcinoma tissues by immunohistochemistry.ResultsWe indentified ten gains and 22 losses in rectal adenoma, and found 25 gains and 14 losses in carcinoma. Gains of 7p21.3-p15.3, 7q22.3-q32.1, 13q13.1-q14.11, 13q21.1-q32.1, 13q32.2-q34, 20p11.21 and 20q11.23-q12 and losses of 17p13.1-p11.2, 18p11.32-p11.21 and 18q11.1-q11.2 were shared by both rectal adenoma and carcinoma. Gains of 1q, 6p21.33-p21.31 and losses of 10p14-p11.21, 14q12-q21.1, 14q22.1-q24.3, 14q31.3-q32.1, 14q32.2-q32.32, 15q15.1-q21.1, 15q22.31 and 15q25.1-q25.2 were only detected in carcinoma but not in adenoma. Copy number and mRNA expression of EFNA1 increased from rectal adenoma to carcinoma. C13orf27 and PMEPA1 with increased copy number in both adenoma and carcinoma were over expressed in rectal cancer tissues. Protein and mRNA expression of GPNMB was significantly higher in cancer tissues than rectal adenoma tissues.ConclusionOur data may help to identify the driving genes involved in the adenoma-carcinoma progression.
| S-EPMC3533962 | biostudies-literature
Project description:IntroductionGenomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution.MethodsWe employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines.ResultsCommon amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by comparative genomic hybridization (CGH) correlated closely with ERBB2 DNA and RNA levels measured by quantitative PCR as well as with ERBB2 protein levels. The overall frequency of recurrent losses was lower, with no region lost in more than 50% of tumors; the most frequently lost tumor suppressor gene was RB1 (hemizygous loss in 26% of tumors). Finally, we find that specific copy number changes in cell lines closely mimicked those in primary tumors, with an overall Pearson correlation coefficient of 0.843 for gains and 0.734 for losses.ConclusionHigh resolution CGH analysis of breast cancer reveals several regions where DNA copy number is commonly gained or lost, that non-random correlations between specific amplicons exist, and that specific genetic alterations are maintained in breast cancer cell lines despite repeat passage in tissue culture. These observations suggest that genes within these regions are critical to the malignant phenotype and may thus serve as future therapeutic targets.
| S-EPMC1410746 | biostudies-literature
Project description:Array comparative genomic hybridization (CGH) has been popularly used for analyzing DNA copy number variations in diseases like cancer. In this study, we investigated 82 sporadic samples from 49 breast cancer patients using 1-Mb resolution bacterial artificial chromosome CGH arrays. A number of highly frequent genomic aberrations were discovered, which may act as "drivers" of tumor progression. Meanwhile, the genomic profiles of four "normal" breast tissue samples taken at least 2 cm away from the primary tumor sites were also found to have some genomic aberrations that recurred with high frequency in the primary tumors, which may have important implications for clinical therapy. Additionally, we performed class comparison and class prediction for various clinicopathological parameters, and a list of characteristic genomic aberrations associated with different clinicopathological phenotypes was compiled. Our study provides clues for further investigations of the underlying mechanisms of breast carcinogenesis.
| S-EPMC5054221 | biostudies-literature
Project description:In this study, we determined the genomic profiles of pancreatic cancer cell lines.
2016-01-22 | GSE65175 | GEO
Project description:In this study, we investigated amplifications and deletions of 49 gastric cancer cell lines by 244k oligonucleotide-based array comparative genomic hybridization.
2016-12-01 | GSE74839 | GEO
Project description:This study comprises arrayCGH data from the University clinic Eppendorf (UKE) in Hamburg. The array platform being used is the VUMC v30 30k Oligo chip
| S-ECPF-MTAB-354 | biostudies-other