Unknown,Transcriptomics,Genomics,Proteomics

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Genotyping of human chromosomal instability patterns discriminates rectal adenomas from carcinomas

ABSTRACT: Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. To identify genetic changes that might correlate with tumour stage and could lead to optimized treatment selection we performed a genome-wide chromosomal instability search in a homogeneous, clinical cohort of rectal tumours. 78 rectal tumours during different clinical stages were analysed with 10K single nucleotide polymorphism (SNP) arrays. Logistic regression was performed to build a quantitative model of specific chromosomal aberrations. Overall, most cases (95%) had one or more chromosomal aberrations. We observed a clear correlation between the total number of aberrations and the different tumour stages. Specifically, the chromosomal events: gain of 8q22â24, 13q and 20q, and loss of 17p and 18q12â22, were far more abundant in carcinoma than in adenoma. In adenoma fractions from cases with a carcinoma (infiltrating at least in the submucosa), twice the amount of such âmalignant aberrationsâ was observed, compared to pure adenomas. Furthermore, combined aberrations such as gain of 13q and loss of 18q were only found in adenomatous fractions of carcinomas and not in benign lesions. Based on these five genomic events associated with carcinoma, a clear distinction between adenoma and carcinoma tissue could be made. These data should be validated further in order that they may be used in preoperative staging of rectal tumours. Experiment Overall Design: 78 tumor samples and 19 reference normal samples

ORGANISM(S): Homo sapiens

SUBMITTER: Hans Morreau

PROVIDER: E-GEOD-7946 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Single nucleotide polymorphism array analysis of chromosomal instability patterns discriminates rectal adenomas from carcinomas.

Lips E H EH de Graaf E J EJ Tollenaar R A E M RA van Eijk R R Oosting J J Szuhai K K Karsten T T Nanya Y Y Ogawa S S van de Velde C J CJ Eilers P H C PH van Wezel Tom T Morreau H H

The Journal of pathology 20070701 3

Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. To identify genetic changes that might correlate with tumour stage and could lead to optimized treatment selection we performed a genome-wide chromosomal instability search in a homogeneous, clinical cohort of rectal tumours. 78 rectal tumo ...[more]

PMID: 17471469

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Project description:Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that loss of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes. We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series (Series GSE7946, Samples GSM194994-GSM195028). We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry. Approximately 8% of the genes were significantly different between adenomas and carcinomas; the most differently expressed genes were involved in cell adhesion and cell cycle processes. Integration of gene expression and chromosomal instability data revealed a significant genome-wide correlation between these two data types. Supervised analysis identified up-regulation of EFNA1 in cases with 1q gain, and EFNA1 expression was correlated with the expression of a target gene (VEGF). The BOP1 gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. SMAD2 was the most down-regulated gene on 18q, and on 20q, STMN3 and TGIF2 were highly up-regulated. Immunohistochemistry for SMAD4 correlated with SMAD2 gene expression and 18q loss. This study showed a good correlation between chromosomal aberrations and gene expression data. In the near future, specific genes identified by such integrative methods could be of additional value for explaining rectal tumorigenesis. Keywords: disease state analysis Samples GSM307294-GSM307372: 79 Tumor RNAs were hybridised, all against a common reference sample, consisting of a mixture of cell line and normal colon RNA. 9 replicates (primarily duplicates) were performed (tumor samples: 217, 544, 608, 609, TME1344, TME625, TME884, TME947).

Dataset Information

Genotyping of human chromosomal instability patterns discriminates rectal adenomas from carcinomas

Publications

Single nucleotide polymorphism array analysis of chromosomal instability patterns discriminates rectal adenomas from carcinomas.

Similar Datasets

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