Exome Sequencing of Normal and Isogenic Transformed Human Colonic Epithelial Cells (HCECs) Reveals Novel Genes Potentially Involved in the Early Stages of Colorectal Tumorigenesis

Exome Sequencing of Normal and Isogenic Transformed Human Colonic Epithelial Cells (HCECs) Reveals Novel Genes Potentially Involved in the Early Stages of Colorectal Tumorigenesis

BMC Genomics, January 2015

25776723

Lu Zhang, Sang Bum Kim, Gaoxiang Jia, Abdelbaset Buhmeida, Ashraf Dallol, Woodring E Wright, Albert J Fornace, Mohammed Al-Qahtani, Jerry W Shay

We have generated a series of isogenically derived immortalized human colonic epithelial cell (HCEC 1CT and HCEC 2CT) lines, including parental un-immortalized normal cell strains. The CDK4 and hTERT immortalized colonic epithelial cell line (HCEC 1CT) is initially karyotypically normal diploid and expresses a series of epithelial cell markers including stem cell markers. Under stressful tissue culture conditions, a spontaneous aneuploidy event occurred in the HCEC 1CT line, resulting in a single chromosomal change leading to a stable trisomy 7 cell line (1CT7). Trisomy 7 occurs in about 40% of all benign human adenomas (polyps) and thus this specific chromosomal change in diploid HCEC 1CT cells appears to be non random. In addition, we have partially transformed the HCEC 1CT line by introducing stable knockdown of wild type APC and TP53, and ectopically introducing a mutant Kras(v12) and a mutant version of APC (A1309), all commonly found mutations in colorectal cancer (CRC).