Genomic landscape of metastatic colorectal cancer.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 25394515.
- Also identified by DOI 10.1038/ncomms6457 and PMC identifier 4243240.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumour biology. Here we describe the genomic landscape of tumour samples of a homogeneous well-annotated series of patients with metastatic CRC (mCRC) of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal subregions are associated with progression-free survival (PFS; uncorrected single-test P-values <0.005). These subregions are filtered for effect on messenger RNA expression, using an independent data set from The Cancer Genome Atlas which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of mCRC reveals a number of DNA copy number aberrations associated with response to drug therapy.
Medical subject headings
- Colorectal Neoplasms
- Genes, Neoplasm
- Genome, Human