Human adenoid cystic carcinoma vs. human normal lymphocyte
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE22328 | GEO | 2011/09/01
SECONDARY ACCESSION(S): PRJNA127529
REPOSITORIES: GEO
Similar Datasets
Project description:We analyzed ten adenoid cystic carcinomas of head and neck by array-based comparative genomic hybridization (a-CGH) using DNA chips spotted 4,030 BAC clones. After data smoothing by the adaptive weights smoothing (AWS) procedure with the gain and loss analysis of DNA (GLAD) algorithm, a total of 89 DNA copy number aberrations (DSCNAs) were detected. The frequent (≥30%) DSCNAs were loss of 6q24, 6q25, 8p23, 6q25, and 6q23 and gains of 6q23, 8p23, 9p11-13, and 22q13. High-level gain was detected on 12q12-15 including MDM2 in two cases. These two cases showed immunohistochemically positive status of MDM2 and negative status of p53 and p21. Furthermore, the total number of DSCNAs was significantly greater in ACC with loss of 6q than in other ACC, in ACC without loss of 8p23 than in other ACC, and in ACC with 8p23 gain than in ACC with 8p23 loss, respectively. Though there is a limit in the evidence, a-CGH detected several candidate chromosomal imbalances associated with DSCNA accumulation in ACC. 6q loss, 12q gain aCGH DNA copy number aberrations screening in human cancer adenoid cystic carcinoma (ACC).
2011-08-31 | E-GEOD-22328 | biostudies-arrayexpress
Project description:Adenoid cystic carcinoma (AAC) is a rare but distinctive tumor. Array comparative genomic hybridization (CGH) has been applied for detecting chromosomal copy number alterations in seventeen frozen salivary or pulmonary ACCs samples. There were recurrent gains at 1p36, 6p21, 16q24, 17q21, and 22q11-13, and recurrent losses at 1p35, 6q22, 8q12-13, 9p21, 12q12-13, and 17p11-13. The minimal common regions (MCRs) of these alterations contained several well-known cancer genes, including TP53, CDKN2A/CDKN2B, SKI, CDK10, and VEGF. CDK10 was the only oncogene that localized to the MCR of gain at 16q24.1-24.3. In addition, we identified LIMA1 as the sole putative tumor suppressor gene residing in the MCR of deletion at 12q12q12-13.2. Among well defined and narrow, but unique alterations, there were gains harboring MDM2, cyclin D1, and KIT, as well as one loss involving the hsa-mir-124a-2 miRNA. Using immunohistochemistry, we found abnormal protein expression in the cases with gain of cyclin D1 or MDM2. In conclusion, the majority of previously reported chromosomal copy number alterations are found using array CGH in this small cohort. The suspicion that genes such as TP53, CDKN2A/CDKN2B, and VEGF might play a role in ACC, is strengthened by our results. CDK10 and LIMA1 emerge from our analysis as candidate cancer genes
2008-04-18 | E-TABM-267 | biostudies-arrayexpress
Project description:Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02 and 0.2 percent of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in approximately 40-70 percent of patients at the time of diagnosis. Standard chemotherapy with mitotane containing regimens is often ineffective and associated with intolerable side-effects. Modern molecular technologies now allow the examination of germ-line and somatic DNA for chromosomal alterations which can give biological insight into cancer processes. Using an array-based high density comparative genomic hybridization (CGH) screen, genomic aberrations within 25 ACC patients were assessed to identify genomic characteristic of this cancer. Genomes were queried with >44,000 probes on the Agilent Human Genome CGH array detecting regions of chromosomal gain and loss within the tumor population. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors. Keywords: CGH, adrenocortical carcinoma, cancer
2007-04-10 | GSE7482 | GEO
Project description:Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02 and 0.2 percent of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in approximately 40-70 percent of patients at the time of diagnosis. Standard chemotherapy with mitotane containing regimens is often ineffective and associated with intolerable side-effects. Modern molecular technologies now allow the examination of germ-line and somatic DNA for chromosomal alterations which can give biological insight into cancer processes. Using an array-based high density comparative genomic hybridization (CGH) screen, genomic aberrations within 25 ACC patients were assessed to identify genomic characteristic of this cancer. Genomes were queried with >44,000 probes on the Agilent Human Genome CGH array detecting regions of chromosomal gain and loss within the tumor population. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors. Experiment Overall Design: Array-based high density comparative genomic hybridization (CGH) screen was utilized to identify genomic aberrations within 25 ACC patients. Thirteen tumor samples are from male and 12 are from female patients. The mean age of patients is 51.8 years (range, 23.3-77.7 years) with a median of 54.2 years. The mean tumor physical measurements for the ACC set are a mean weight of 536.3 grams (range, 20.5-2880 grams) and size of 10.7 cm (range, 3-21.5 cm). The clinical data also includes functional status of the tumor which is based on clinical parameters and confirmed by biochemical analysis. Nonfunctional tumors or those that do not over-produce hormones represent 48% of the tumor set. The localization of each tumor is a measure of the tumor metastatic characteristic at time of operation while tumor grade is a histologically based rating system for tumor progression. Sixty percent of the tumors (15 of 25) were localized to the adrenal area with no indication of metastatic spread. The majority of tumors were grade 3 and 4 at time of diagnosis (17 of 25) indicating necrosis and atypical mitosis of >21/50 hpf. Genomes were queried with >44,000 probes on the Agilent Human Genome CGH array detecting regions of chromosomal gain and loss within the tumor population.
2008-06-15 | E-GEOD-7482 | biostudies-arrayexpress
Project description:We superimposed array comparative genomic hybridization (aCGH) data onto existing expression array profiles (GSE3892) to sift out the pivotal genes underlying the pathogenesis of a well defined series of diffuse large B-cell lymphomas (DLBCL). 280 gained and over-expressed genes were identified, located on chromosomes 1q, 3q, 7, 12p12, 18q and 21q. At the most frequently gained region the oncogene MDMX/MDM4 was concurrently over-expressed, which is a critical regulator of p53 function. In regions of frequent chromosomal loss, 36 genes were concurrently down-regulated, restricted to 6q and 15p. These putative tumor suppressor genes included PERP, MAP3K5, CCNDBP1 and β2M, and loss of 6q was associated with poor clinical outcome. Genes identified and chromosomal regions validated in an independent series of DLBCL patients. Overall design fields: Copy number profiles (array CGH) of a series of 42 Diffuse large B-cell lymphoma patient samples were analyzed a) for frequency of aberrations and b) for impact on gene expression. No duplicate samples or dye-swaps were analyzed. a) Statistical analysis of Array CGH data Calling: Areas of gains and losses and their frequencies throughout the dataset were determined from the Bluefuse ratios within the statistical package â??CGHcallâ?? (van de Wiel et al., 2007). Briefly, after smoothing outliers and median normalization, â??DNAcopyâ?? segmentation (Olshen et al., 2004) was applied within CGHcall, after which a call was assigned to each position on the genome. Within CGHcall the probabilities of the calls were determined per chromosomal arm, and a cellularity correction of 0.75 was applied to each sample because tumor cellularity in all DLBCL is estimated to be maximal 75%, taking into account all stromal, endothelial en infiltrating lymphocytes. After calling, we applied â??CGHregionsâ?? (van de Wiel and van Wieringen 2007) to determine regions of consecutive clones with highly similar calls for all samples. This dimension reduction further increases robustness and statistical power for downstream statistical analyses. Called data were used for all downstream analyses. b) Integration with expression data To integrate called array CGH data with expression array data, the array CGH and expression integration tool, ACE-it (van Wieringen et al., 2006), was used. For ACE-it analysis chromosomal amplifications were included in the gains. ACE-it uses the one-sided Wilcoxon rank sum to test which chromosomal aberrations recurrently affect RNA expression and adjust p-values for multiple testing. Only those clones were taken into account which had at least 20% (9) of the samples in one of the other calling states (gain or loss). Only genes were considered relevant with a false discovery rate of <0.1. References - Olshen AB, Venkatraman ES, Lucito R, Wigler M (2004) Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics 5: 557-72. - van de Wiel MA, Kim KI, Vosse SJ, van Wieringen WN, Wilting SM, Ylstra B (2007) CGHcall: calling aberrations for array CGH tumor profiles. Bioinformatics 23: 892-4. - van de Wiel MA, van Wieringen WN. CGHregions: dimension reduction for array CGH data with minimal information loss. Cancer Informatics. In press 2007. - van Wieringen WN, Belien JA, Vosse SJ, Achame EM, Ylstra B (2006) ACE-it: a tool for genome-wide integration of gene dosage and RNA expression data. Bioinformatics 22: 1919-20.
2010-06-25 | E-GEOD-5138 | biostudies-arrayexpress
Project description:RNA-sequencing was performed to gain insight into the mechanism responsible for the apoptosis and cell cycle arrest induced by loss of Mdm2 in p53-null cells. Following CreERT2-mediated deletion of Mdm2 in three p53-null cell types (T cell lymphoma, sarcoma, and fibroblasts), RNA-sequencing was performed. This high-throughput data revealed Mdm2 deletion in p53-null cells upregulated p53/p73 transcriptional target genes known to induce apoptosis and cell cycle arrest.
2017-09-06 | GSE98705 | GEO
Project description:Ependymoma (EPN) posterior fossa group A (PFA) has the highest rate of recurrence and the worst prognosis of all EPN types. At relapse, it is typically incurable even with re-resection and re-irradiation. The biology of recurrent PFA EPN remains largely unknown, which hinders clinical advances. In this large longitudinal multicenter study, we examined matched samples of primary and recurrent disease from PFA EPN patients (n=95) to investigate the biology of recurrence. DNA methylomic data was used to measure copy number variants (CNVs), revealing progressive large scale chromosome gains and losses in successive recurrences. These CNV changes were dominated by chromosome 1q gain and/or 6q loss (1q+/6q-), both previously identified as high-risk factors in PFA EPN, which were present in ~20% at presentation but increased to ~60% at 1st recurrence. These CNV changes were correlated with hypomethylation of heterochromatin associated DNA at presentation. Evolution of chromosomal aberrations was further explored using CNV analysis of single-nuclei RNAseq on approximately 46,000 PFA EPN cells from 6 matched pairs of primary and 1st relapse tumors that harbored CNV changes at recurrence. No evidence of rare subclones in primary tumors was observed, suggesting that chromosomal rearrangement events occur after initial presentation. Cellular and molecular characteristics associated with CNVs were examined by single-nuclei RNAseq, bulk transcriptomic analysis and immunohistochemistry, revealing that 1q+/6q- PFA have a significantly higher mitotic index, increased proportions of proliferative epithelial progenitors and decreased differentiated neoplastic subpopulations. Multivariate survival analyses showed that cases with 1q gain or 6q loss at 1st recurrence were significantly more likely to recur than cases with no 1q or 6q change. The high prevalence of 1q+/6q- at recurrence and the associated shortened survival, suggest that both these abnormalities should be routinely tested for, and used for trial stratification.
2023-06-01 | GSE227644 | GEO
Project description:Two distinct groups of posterior fossa ependymoma, PF-EPN-A and PF-EPN-B have been identified in children and are often associated with widely distinct outcomes. We have identified an ultra-high-risk PF-EPN-A ependymoma with 6q loss. We performed RNA sequencing of posterior fossa ependymoma A (PF-EPN-A) tumor samples with chromosome 6q loss and balanced to understand the differences in 6q loss at the transcriptomic level
2021-02-15 | GSE164292 | GEO
Project description:With an objective to identify novel copy number alterations (CNAs) critical to CLL pathogenesis, we performed array comparative genomic hybridization (array CGH) on genomic DNA extracted from purified leukemic cells of 51 CLL patients. We used the 1.4 Mb HumArray platform, and analyzed data using a combination of three different statistical algorithms and in full awareness of the copy number variations (CNVs) found in normal populations. Use of reference DNA extracted from matched patient neutrophils in four cases also assisted a more comprehensive interpretation of constitutional versus CLL-specific copy number alterations. A total of 108 clones showed alterations in >10% of the cases. Of these, 25 clones corresponded to known recurrently acquired CNAs for CLL, representing +12 in 8 cases (16%) and del(13)(q14) in 26 cases (51%). For the remaining 83 clones, frequent deletions corresponded to loci within cytobands 17q12 (71% of CLL cases), 9q32 (55%), 8p23 (47%) and 2q21 (33%), and frequent gains corresponded to loci within cytobands 18q22.3 (51%), 20p12 (33%) and 15q13 (31%), most of which have been reported in normal population cohorts. We further analysed associations between CNV status across the 108 frequently affected clones and CD38 expression status. Consistent with previous findings, loss of 13q14 (represented in clone RPI-269F22) and gain of chromosome 12 (clones RP11-64J22, RMC12P001 and RP11-282G15) were associated with low and high CD38 expression, respectively. We also found that loss within the beta-defensin (DEFB) locus at 8p23, and gains across clones CTB-120N12 (17q25) and RP11-118K20 (13q31.1) were associated with the poor prognostic CD38+ subgroup (p<0.05). Further studies are needed to assess biological relevance of genes located within these regions and prognostic outcomes in CLL.
2017-06-14 | GSE21998 | GEO