Molecular subtype assay to reveal anti-EGFR response sub-clones in colorectal cancer (CRC).

658Background: We previously stratified CRC into five intrinsic gene expression subtypes (CRCAssigner) and four consensus molecular subtypes (CMS1-4) using expensive and time-consuming microarray/RNAseq platforms. Recently, we developed a low-cost (NanoCRC) assay using nCounter platform (NanoString Technology) and robust gene signatures to classify individual samples into both CRCAssigner and CMS subtypes. Here, we tested the assays using formalin-fixed paraffin-embedded (FFPE) patient samples from Royal Marsden Hospital. Given increased sensitivity to cetuximab in one of our CRCAssigner subtypes transit-amplifying (TA) that represents partly CMS2 subtype, we associated anti-EGFR response to the presence of TA sub-clones. Methods: FFPE from resected and biopsy CRC samples were profiled for our NanoCRC assay. Along with our single-sample subtyping method, we developed a tool to identify sub-clones of TA within individual samples. RAS/BRAF wild-type patients treated with single agent anti-EGFR therapy were ...