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Prevention and Early Detection Biomarkers of Adenomas and CRC Lesions During CRC Screening

ABSTRACT: The investigators designed a prospective study to evaluate the predictive ability of detection of mutations in genes involved in carcinogenesis of the colon (eg hMLH1, K-Ras, B-Raf, ccfDNA) in a sample of Greek population presents for conducting colonoscopy in the context of screening under international CRC prevention instructions. This investigation will be carried out in individuals in normal risk in order to study specific mutations (in blood and tissue) to draw reliable conclusions about whether we can detect (with greater sensitivity and specificity) patients with precancerous lesions or CRC with a simple blood test thereby reducing the cost and side effects of repeated endoscopic procedures.

DISEASE(S): Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2201662 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Background: In vitro models are an essential tool towards understanding the molecular characteristics of colorectal cancer (CRC) and the testing of therapies for CRC. To this end we established 21 novel CRC cell lines of which six were derived from liver metastases. Extensive genetic, genomic, transcriptomic and methylomic profiling was performed in order to characterize these new cell lines and all data is made publically available. Additionally, sensitivity of oxaliplatin was tested as a measure for chemotherapy resistance. Results: DNA copy-number alterations (CNA) were compared between primary and metastasis derived cell lines. In concordance with previous studies copy-number gain of chr20, and loss of chr8p were found highly specific for liver metastases. Previously reported BRAF-mutation associated DNA methylation profiles could be validated on the genome-wide DNA methylation profiles of these cell lines. 47.6% of the loci previously reported to associate with BRAF mutation status were reproduced in this dataset. When examining the gene expression profiles in conjunction with these DNA methylation results, we identified 20 genes of which the gene expression correlated with the DNA methylation status, including MEIS1, LRAT and STC2. These genes have previously been reported to be subject to transcriptional regulation through DNA hypermethylation, validating our approach. Conclusions: By combining mutation profiles with CNA and gene expression profiles we constructed an overview of the alterations in the major CRC-related signalling pathways. The mutation profiles, along with the genome, transcriptome and methylome data of these cell lines will be made publically available . This combined dataset puts these cell lines among the best characterized CRC cell lines, allowing researchers to select appropriate cell line models for their particular experiment, making optimal use of these novel cell lines as in vitro model for CRC. 21 CRC cell lines were analyzed

Dataset Information

Prevention and Early Detection Biomarkers of Adenomas and CRC Lesions During CRC Screening

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