Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

SOX2 is a new oncogene activated by the recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE14859: ArrayCGH mapping of chromosome 3 aberrations in lung Squamous Cell Carcinoma (SCC) GSE14883: SOX2 overexpression effect on human lung squamous cells GSE15079: ArrayCGH mapping of the recurrent 3q26.3-q27mplifications in lung Squamous Cell Carcinoma (SCC) Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Thomas Hussenet

PROVIDER: E-GEOD-15080 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.

Hussenet Thomas T Dali Soraya S Exinger Julien J Monga Ben B Jost Bernard B Dembelé Doulaye D Martinet Nadine N Thibault Christelle C Huelsken Joerg J Brambilla Elisabeth E du Manoir Stanislas S

PloS one 20100129 1

Squamous cell carcinoma (SCC) of the lung is a frequent and aggressive cancer type. Gene amplifications, a known activating mechanism of oncogenes, target the 3q26-qter region as one of the most frequently gained/amplified genomic sites in SCC of various types. Here, we used array comparative genomic hybridization to delineate the consensus region of 3q26.3 amplifications in lung SCC. Recurrent amplifications occur in 20% of lung SCC (136 tumors in total) and map to a core region of 2 Mb (Megaba ...[more]

PMID: 20126410

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Project description:Cervical cancer develops from pre-cancerous high-grade cervical intraepithelial neoplasia (CIN) lesions harbouring a transforming infection with high-risk human papillomavirus (hrHPV), which is characterised by p16INK4a overexpression. Since it takes one or more decades for these pre-cancerous lesions to progress to invasive squamous cell carcinomas (SCCs), it is obvious that they are heterogeneous in terms of duration of existence and progression risk. We performed array-based comparative genomic hybridisation (array CGH) of 46 p16INK4a immuno-positive CIN2/3 lesions to determine whether this heterogeneity is reflected in their chromosomal profiles. Chromosomal profiles of CIN2/3 lesions were related to those of invasive cervical squamous cell carcinomas (SCCs) and promoter methylation of the CADM1 gene, a tumour suppressor gene known to be functionally involved in the tumorigenic phenotype of cervical cancer cells. Frequent alterations found in CIN2/3 lesions included gains located at chromosome 1, 3, 7 and 20 and losses located at 4, 11, 16, 17 and 19. Unsupervised hierarchical clustering identified two subsets of CIN2/3 lesions, chromosomal profiles of one of which closely resembled invasive SCCs. Gains of 1, 3q and 20 were characteristic for CIN2/3 lesions with chromosomal signatures resembling carcinomas. In addition, dense promoter methylation of the CADM1 gene was significantly more frequent in these CIN2/3 lesions (p=0.004). No chromosomal alterations were detected in one p16INK4a positive and five p16INK4a negative CIN1 lesions. These findings suggest that biomarkers associated with gains at chromosomes 1, 3q and 20 are potential hallmarks of advanced p16INK4a positive CIN2/3 lesions with a high short-term risk of progression. Genomic DNA of 46 high-grade cervical lesions was hybridised to 5K CGH BAC microarrays (5K) produced at the Microarray facility of the VU Medical Center. In total 4632 BAC clones with known chromosomal location were spotted in triplicate, which included the 1Mb resolution Sanger BAC clone set and a subset of clones from the Children’s Hospital Oakland Research Institute (CHORI). All samples were labelled with Cy3 and hybridised together with a pool of normal male reference DNA labelled with Cy5. Hybridisations were essentially performed as described by Snijders et al (Nature Genetics 2001). Both pre-hybridisation and hybridisation were performed in a hybridisation station (HybStation12 – Perkin Elmer Life Sciences). Hybridised arrays were scanned using a G2505B scanner (Agilent, Wilmington, DE, USA). Spots were quantified using ImaGene 5.6.1 software (BioDiscovery Ltd, Marina del Rey, CA, USA) with default settings for the flagging of bad quality spots. Genomic DNA of 6 CIN1 lesions was hybridised on CGH oligo microarrays (44K) produced by Agilent following the manufacturer’s protocol against the same normal reference pool. Hybridised arrays were scanned using the same scanner (G2505B, Agilent). Quantification of these arrays was done using Feature Extraction software version 9.5.1 (Agilent).

Project description:A better understanding of the consequences of recurrent (epi)genetic alterations that occur during cervical carcinogenesis is essential in the search for novel biomarkers. In this study we determined genome-wide expression profiles of 10 squamous cell carcinomas (SCCs), 5 adenocarcinomas (AdCAs) and 6 normal epithelial samples. Expression patterns were subsequently combined with previously determined chromosomal profiles in the same carcinomas. Differential gene expression analysis identified 76 genes with altered expression in carcinomas compared to normal epithelium. Microarray results for a subset of these genes were validated by real-time RT-PCR. Among the differentially expressed genes a relative overrepresentation of genes located at chromosome 3q, one of the most frequently gained areas in SCCs, was observed (false discovery rate (FDR)<0.005). To further investigate the relationship between gene expression and chromosomal alterations 2 statistical approaches were used, i.e. differential gene locus mapping (DIGMAP) and the array CGH expression integration tool (ACE-it). Using these methods we found that increased gene expression was linked to increased gene copy numbers at 1q32.1, 3q13.32-22.3, 3q26.32-27.3, and 20q11.21-13.33, whereas a loss at 11q22.3-25 correlated with recurrent decreased gene expression. Integrated genome-wide chromosomal and transcriptional analysis of cervical carcinomas highlighted 7 genes (i.e. FLJ21291, DTX3L, CCDC14, MCM2, PIK3R4, ATP2C1 and SLC25A36), which were identified by differential gene expression analysis and were located within the chromosomal regions identified by DIGMAP and/or ACE-it as well. Further investigations of these promising marker genes in warranted. Keywords: microarray analysis, array CGH, cervical cancer For microarray mRNA expression analysis 10 SCCs, 5 AdCAs and 6 normal epithelial controls were used. Normal cervical controls consisted of 1 pool of 3 normal cervices distant from tumour, 1 pool of 4 normal ectocervical smears and 1 pool of 5 normal endocervical smears. To expand our number of normal squamous epithelial controls, we included expression profiles of 3 uvulas of non-cancer patients who underwent uvulopalatopharyngoplasty. In addition, we hybridised RNA isolated from 2 different biopsies of the same SCC (SCC12 and SCC13) as a biological replicate. The pool of 4 normal ectocervical smears was hybridised twice as a technical replicate to determine technical variation. Genomic profiling of the same 10 SCCs and 5 AdCAs was done using array CGH (Wilting et al, J Pathol 2006, volume 209, p 220-30).

Dataset Information

SOX2 is a new oncogene activated by the recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma

Publications

SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.

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