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Characterisation of genome-wide copy number aberrations in colon cancer

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Introduction : Despite improved screening programs and modern treatments, colorectal cancer (CRC) still remains the third most common cancer in men and women and the second leading cause of cancer-related death. The development of CRC is characterised by several genetic and epigenetic alterations. There is still a high rate of recurrence and metastases with a remaining need for identification of molecular biomarkers in order to predict the evolution of the disease. Aim : Our aim was to characterise copy number alterations in different subgroups of colon cancer patients. Methods : Genetic alterations were analysed using Array Comparative Genomic Hybridisation (array-CGH) in 100 resection tissues of colon tumours. The tumour DNA was isolated with the Qiagen DNeasy Blood and Tissue kit. Megapool reference DNA was used as normal control. Tumour DNA was labelled with the fluorescent dye Cy3 and the normal control was labelled with Cy5. After labelling the DNA, it was hybridised to a SurePrintG3 Human CGH Microarray, 4 × 180 K. The scanned images were analysed with an in-house developed software program, arrayCGHbase. Results : In the studied patient population, 3-year survival and recurrence of disease were correlated with the stage of colon cancer but not with tumour localisation. Preliminary results showed a significant correlation (p < 0,001) between the number of genetic alterations and overall survival of the patients (n = 100). The most prevalent copy number alterations in CRC as described in literature, were confirmed in our samples, for instance gain of chromosomes 7, 13 and 20 and losses of chromosomes 4 and 18. Moreover, we found alterations residing in a number of new interesting chromosome regions. Future analyses will have to reveal the clinical relevance in colon. cancer. Conclusion : The number of copy number alterations is associated with the overall survival of colon cancer patients. The new findings will be further investigated in depth. The link between KRAS and MSI status and the copy number alterations in the tumours will also be investigated.
Boek: ACTA GASTRO-ENTEROLOGICA BELGICA
Volume: 76
Aantal pagina's: 1
Jaar van publicatie:2013