Genetic and epigenetic changes and their effect on prognosis and prediction of colorectal cancer — ASN Events
  1. Schedule
  2. Poster discussion 2
  3. Genetic and epigenetic changes and their effect on prognosis and prediction of colorectal cancer

Genetic and epigenetic changes and their effect on prognosis and prediction of colorectal cancer (#367)

Arpad Bóday 1 , Spiros Tavandzis 1 , Veronika Krhutova 1 , Kateřina Horka 1 , Hana Dvorakova 1 , Pavla Vanickova 1 , Jarmila Ryskova 2 , Alice Janeckova 2 , Martin Nemecek 3 , Ivo Kaspercik 3
  1. Laboratory of Medical Genetics - Department of Molecular Biology, AGEL Research and Training Institute - Nový Jičín Branch, AGEL Laboratories, Nový Jičín, Czech Republic
  2. Radiotherapy and Clinical Oncology, Comprehensive Cancer Center, AGEL a.s., Nový Jičín, Czech Republic
  3. Laboratory of Pathology, AGEL Research and Training Institute - Nový Jičín Branch, AGEL Laboratories, Nový Jičín, Czech Republic

Background:

Development of colorectal cancer (CRC) is a multi-step process. It includes a range of different molecular events that are causing gradual conversion of epithelium to carcinoma by three relatively well defined pathways.

Aim:

The aim of this work was the genetic and epigenetic characterization of CRC in group of 267 patients.

Methods:

DNA was isolated from frozen tumor and healthy tissues. MSI and LOH were studied in 8 loci. Mutation analysis were focused on genes K-ras, BRAF, PIK3CA, APC and TP53. Methylation status was analyzed in genes hMLH1, APC, CDKN2A, TP53, MGMT and loci MINT1, MINT2, MINT17, MINT31. The effect of various genetic and epigenetic changes in relation to the survival length was evaluated by Kaplan-Meier survival analysis.

Results:

Pathogenic mutations in genes K-ras, BRAF, PIK3CA, APC and TP53 were detected in the analyzed group of 267 CRC patients with mutation frequencies of 38.5%, 6.8%, 7.2%, 39% and 12%, respectively. MSI was found in the 10.5% of carcinomas. LOH was determined in genes APC, hMSH2, BRCA1, DCC, c-Kit and HSD3B1 with the following frequencies: 11.6%, 3.4%, 3.4%, 4.1%, 1% and 0.8%. Hypermethylation was detected in APC (37.2%), hMLH1 (18.5%), TP53 (11.8%), CDKN2A (15.7%), MGMT (31.5%) genes and MINT1 (27.1%), MINT2 (42.9%), MINT17 (8.9%), MINT31 (17.8%) loci.

Conclusions:

In this study, we present results of genetic and epigenetic analysis performed on tumor samples and we speculate about the classification of the CRC patients into different molecular subtypes within the context of pathological, histological and immunohistochemical results. Results are consistent with published data and they confirm that the biological nature and progression of colorectal cancer is determined by total accumulation of molecular changes, rather than a sequence of events. CRC does not have its own unique methylation status, but a combination of several epigenetic features can successfully predict the prognosis of the disease.

#COSAASM