Methylation profiling of locally advanced rectal cancer (LARC): Exploration of potential predictive markers for neoadjuvant chemoradiation (NACR).

614 Background: NACR followed by total mesorectal excision (TME) is standard of care for LARC. However, only 10-20% of patients achieve complete pathologic response with associated optimal clinical outcome. No predictive biomarker is currently available. Aberrant DNA methylation is well known for its key role in the pathogenesis of colorectal cancer. Previous rectal cancer methylation studies were conducted in patients without NACR or inconclusive. We hypothesized a correlation between methylation status and pathologic outcome following NACR. Methods: This is an IRB approved, retrospective, translational study of patients with LARC who received identical NACR before TME at New York University hospitals. Ten micron sections from FFPE tissue blocks underwent laser capture microdissection (LCM) followed by genome DNA isolation. Illumina Infinium 450k methylation array was used to assess 485,000 methylation sites. Methylation profiles and copy number changes were analyzed using in-house bioinformatics. Histon...