P-204 - Array-comparative genome hybridization analysis of primary colorectal cancers and corresponding liver metastases

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter J. Zurawska
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors J. Zurawska, J. Kisluk, B. Kedra, O. Kowalczuk
  • Medical University of Białystok, Białystok/PL

Abstract

Introduction

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. The major cause of death in patients with CRC are metastases, particularly to the liver, found in up to 25% of the patients at primary diagnosis and occurring in the majority of the remaining patients during the following disease course. Despite intensive investigations, molecular mechanisms of metastasis development remains poorly understood. Modern high throughput methods that allow a comprehensive analysis of the cellular genome structure and activity seem to be very helpful in the elucidation of these mechanisms. The aim of the present study was to use an array-comparative genome hybridization method (aCGH) to asses chromosomal aberrations in primary colon tumors and consequent liver metastases.

Methods

Six primary adenocarcinomas (two from the colon and four from the rectal) and matched liver metastases were included into the study. Normal colon mucosa were used as a control. All the tissues were obtained intraoperatively from IV-staged CRC patients. The patients include two females and four males aged from 37 to 50. Before DNA extraction cryo-sections of each frozen sample was evaluated by an experienced pathologist, and only highly rich in cancer cells specimens (>90%) were used. DNA was isolated with a DNeasy Blood & Tissue Kit (Qiagen) according to producer's protocol. Whole-genome chromosomal aberrations were identified by aCGH method using Sure Print G3 Human CGH 8x60K Oligo Microarrays. Microarrays were scanned on a High- resolution scanner G2505C. Row fluorescent data were processed with a Feature Extraction Software v. 12.0, and chromosomal aberrations were identified with a CytoGenomics v. 3.0 Software (all products from Agilent Technologies).

Results

Five of the analyzed primary tumors exhibited numerous chromosomal aberrations that include losses in 3p, 4q, 5p, 6q, 8p, 10q, 11q, 13q, 14q, 17q, 17p, 18q, 18p, 20q, 20p and gains in 11q, 13q, 13p, 17q, 20q, 20p. Loss or gain of a whole chromosomal arm was frequently observed. The most frequent change was a 16p11.1 deletion demonstrated in 3 out of 6 tumors. A number of chromosomal imbalances in corresponding liver metastases was significantly lower than in primary tumors, and only not numerous similar changes were observed in matched primary tumors and metastases. These included gains of 11q13.33-q13.4, 13q12.11-q34.2, 20q11.21-q13.32, 20p11.1-p11.21, 20q11.21-qter and losses of 3p11.2-p25.5, 3p14.3, 6q14.3-q23.2, 8p12-pter, 11q13.4-q25, 14q11.2-q32.31, 17p11.1-p13.3, 18q21.2-q23, 20p11.21-p13. In one primary tumor, we did not observed any chromosomal changes while a corresponding liver metastasis surprisingly demonstrated numerous aberrations.

Conclusion

Our results suggest that a significant genome disruption is characteristic for the majority of the advanced CRCs, although tumors with stable genome also exist. Metastasis development probably occurs before genome imbalance. Analysis of the chromosomal aberrations common for primary tumors and metastases may be helpful in searching for metastasis-related genes.