Genomic copy number aberrations in primary lung squamous cell carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dongmei Lin
PROVIDER: E-GEOD-43131 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Purpose: Only a limited number of genetic studies have been performed in primary central nervous system lymphomas (PCNSL), partly due to the rarity of the tumors and the very limited amount of available tissue. In this report, we present the first molecular characterization of copy-number abnormalities (CNA) of newly diagnosed PCNSL by array-based comparative genomic hybridization in formalin fixed paraffin embedded (FFPE) specimens and compare the results with matched frozen tumor specimens. Experimental design: We performed array-based comparative genomic hybridization (aCGH) in FFPE tissues from PCNSL. Results were compared with matched paired frozen tumors. Results: Our analysis confirmed the good to fair quality and reliability of the data generated from limited amounts of tumoral FFPE tissue. Overall, all PCNSL cases were characterized by highly complex karyotypes with a median of 23 copy-number abnormalities (CNA) per patient (range 17-47). Overall, 20 chromosomal regions were recurrently found in more than 40% of cases. Deletions of 6p21, 6q, 9p21.3 and gain of 12q12-q24.33 were the commonest CNA. Other minimal affected regions were defined, and novel recurrent CNAs affecting single genes were identified in 3q26.32 (TBL1XR1) and 8q12.1 (TOX). Conclusions: The results obtained are encouraging. Larger archival tissue collections can now be analyzed in order to complement the still fragmented knowledge we have of the genetic basis of the PCNSL. We included samples from 7 PCNSL patients. In 6 out of these 7 PCNSL patients (cases B – G), aCGH experiments were performed in DNA samples obtained from both snap-frozen and FFPE tissues for assay quality comparative purposes. In the remaining sample (case A), only frozen sample was analyzed.
2012-04-29 | E-GEOD-28952 | biostudies-arrayexpress
Project description:Chromosomal instability is one of the hallmarks of tumors, which can result in the gain or loss of specific genomic regions or even entire chromosomes. These copy number aberrations (CNAs) play an important role in carcinogenesis and malignant progression through CNA-induced gene expression alterations and, subsequently, key cancer-specific processes. In the current study, we applied aCGH analysis to screen out CNAs with potential prognostic value in lung SCC patients.
2015-09-22 | GSE43131 | GEO
Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 400K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 30 gastric cancer patients. Whole genomic CNAs in 30 human gastric cancers were analyzed using the Agilent aCGH-400K arrays. Matched normal tissues were used as the reference.
2015-05-28 | E-GEOD-69266 | biostudies-arrayexpress
Project description:In this study, we evaluation of incidence of copy number abnormalities (CNAs) with high-desity CGH+SNP microarrays in cohort 26 patients with cervical tumors. Incidence of CNAs was copmared with clinical prognostic factors.
2014-04-01 | E-MTAB-2293 | biostudies-arrayexpress
Project description:We investigated a cohort of 34 archival cutaneous melanoma samples by Agilent 40 kb-resolution CGH array. We found a non-random distribution of precise CNAs predictive for clinical outcome. Although most of the alterations defined in this study have been already reported, we mapped novel melanoma-specific CNAs at highest accuracy. Moreover, our data revealed distinct amplifications hotspots, some of which were validated by quantitative real-time PCR, enabling the identification of novel melanoma oncogenic candidates. Keywords: Cutaneous melanoma, Copy number alterations, Biomarkers, FFPE We examined 34 primary melanoma formalin-fixed and paraffin-embedded (FFPE) samples by using array comparative genomic hybridization (aCGH) for DNA copy number alterations (CNAs). Genomic DNA was extracted, referred to a sex-matched diploid commercial control DNA (Promega Corporation, Madison, WI, cat. G1417 and G1521), and hybridized on the Agilent SurePrint G3 Human CGH Microarray 8x60k, cat. G4827A.
2013-07-01 | E-GEOD-45354 | biostudies-arrayexpress
Project description:Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses, to track tumorsâ genetic evolution and to investigate the genetic background of DLBCL recurrence. Three clonally-unrelated DLBCL relapses were identified (15%). Also, two distinct patterns of genetic evolution in clonally-related relapses were detected: (1) early-divergent/branching evolution from a common progenitor in 6 patients (30%), and (2) late-divergent/linear progression of relapses in 11 patients (65%). Analysis of recurrent genetic events identified potential early drivers of lymphomagenesis (KMT2D, MYD88, CD79B and PIM1). The most frequent relapse-specific events were additional mutations in KMT2D and alterations of MEF2B. SOCS1 mutations were exclusive to non-relapsing DLBCL, whereas primaries of relapsing DLBCL more commonly displayed gains of 10p15.3-p12.1 containing the potential oncogenes PRKCQ, GATA3, MLLT10 and ABI1. Altogether, our study expands knowledge on clonal relationship, genetic evolution and mutational basis of DLBCL relapses. There are 62 copy number Agilent 180k SurePrint arrays in total, which represent 40 cases. There are 21 arrays of primary relapsing DLBCL tumors, 21 arrys of matched relapses and 20 arrays of non relapsing DLBCLs.
2016-06-01 | E-GEOD-65720 | biostudies-arrayexpress
Project description:Neuroblastoma (NB) is an aggressive tumor that affects both infants and children. The disease outcome is greatly influenced by age of patient, stage, chromosome copy number aberrations (CNAs) and gene expression abnormalities. We analyzed, by microarray technology, genome and transcriptome of 3 groups of tumors of patients with metastatic disease: G1, stage 4S and MYCN single copy; G2, stage 4 younger than 18 months of age, MYCN single copy with no disease progression and G3, stage 4, older than 19 months, with unfavorable outcome. We found an accumulation of structural copy number aberrations (CNAs) in G3 whereas G1 tumors had mostly numerical (N) CNAs and G2 showed an intermediate behavior. Pair wise comparisons demonstrated that the average of N CNAs significantly decreased from G1 to G2 to G3 (9.6 G1 < 7.2 G2 < 3.6 G3); in contrast S CNAs significantly increased in G3 (0.7 G1 < 3.7 G2 < 7.0 G3). Interestingly, we observed several intra-chromosomal rearrangements in G3 tumors on chromosomes not usually involved in NB. Excluding MYCN amplified tumors by G3 we found a high frequency of S CNAs in this group. Gene expression analysis showed a deregulation of downstream genes of Ras and Rho signaling pathway among the 3 groups. It has been also observed a progressive switch off of development and adhesion genes and a switch on of cell cycle genes from G1 to G2 to G3. Moreover, the telemorase genes were significantly expressed in G3 with respect to remaining groups. Present data show an accumulation of S CNAs from stage 4S to 4. The deregulation of genes Rho/Ras pathway may explain the increase of tumor aggressiveness from G1 to G2 to G3. The increase of cell cycle and telomerase genes expression associated with G3 would provide unlimited replicative potential for these tumors and may be responsible for accumulation of S CNAs. Finally, we can argue that accumulation of structural aberrations and gene deregulation is age-dependent and it is associated with a more aggressive tumor phenotype. We analyzed 133 samples of metastatic neuroblastoma from patients divided into three groups: G1 49 patients stage 4S and MYCN single copy; G2 37 patients stage 4 younger than 18 months of age at diagnosis, MYCN single copy with no disease progression; G3 47 patients stage 4 older than 19 months of age at diagnosis, with unfavorable outcome.
2012-01-01 | E-GEOD-25771 | biostudies-arrayexpress
Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 400K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 30 gastric cancer patients.
2015-05-28 | GSE69266 | GEO
Project description:Copy number alteration (CNA) is a good signpost to identify cancer related genes. CNAs were analyzed using the Agilent 244K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 10 gastric cancer patients.
2015-05-29 | GSE69318 | GEO
Project description:Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) present in 48 clear cell renal cell carcinoma (ccRCC) genomes result in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes are mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs are classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turn out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. Finally, the diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) are successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreases with the number of G3 related gene losses plus the total number of gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.
2017-06-09 | GSE95239 | GEO