Tumor genome wide DNA alterations assessed by array CGH in patients with poor and excellent survival following operation for colorectal cancer. Cancer Informatics

Abstract: Genome wide DNA alterations were evaluated by array CGH in addition to RNA expression profi ling in colorec-tal cancer from patients with excellent and poor survival following primary operations. DNA was used for CGH in BAC and cDNA arrays. Global RNA expression was determined by 44K arrays. DNA and RNA from tumor and normal colon were used from cancer patients grouped according to death, survival or Dukes A, B, C and D tumor stage. Confi rmed DNA alterations in all Dukes A – D were judged relevant for carcinogenesis, while changes in Dukes C and D only were regarded relevant for tumor progression. Copy number gain was more common than loss in tumor tissue (p 0.01). Major tumor DNA alterations occurred in chromosome 8, 13, 18 and 20, where short survival included gain in 8q and loss in 8p. Copy number gains related to tumor progression were most common on chromosome 7, 8, 19, 20, while corresponding major losses appeared in chromosome 8. Losses at chromosome 18 occurred in all Dukes stages. Normal colon tissue from cancer patients displayed gains in chro-mosome 19 and 20. Mathematical Vector analysis implied a number of BAC-clones in tumor DNA with genes of potential importance for death or survival. The genomic variation in colorectal cancer cells is tremendous and emphasizes that BAC array CGH is presently mor