Genetic analysis of colorectal cancers in young patients.

632 Background: The incidence of colorectal cancer (CRC) is increasing in adults <50 years old and these cases may be associated with a worse prognosis. Despite our growing understanding of genetic conditions, a substantial number of CRC in young patients are classified as sporadic but may harbor unique molecular changes. We sought to compare profiles of genetic alterations between young and old patients who lack defects in known hereditary cancer genes. Methods: 283 CRC cases diagnosed between 1998 and 2010 were analyzed by targeted exome sequencing using the Illumina NGS platform with 50-100x coverage. Filtering of normal variants was performed using 1000 Genomes to enrich for somatic mutations which were then limited to those predicted to alter protein sequence. The younger and older cohorts were defined as ≤45 and ≥65 years old at diagnosis, respectively. Patients found to be MSI-high (n= 2 young, 50 old) or with a known hereditary syndrome (n=6) were excluded. For this preliminary screen, Fisher’s Ex...