Consensus molecular subtypes in colorectal cancer differ by geographic region.

Abstract

4061 Background: The consensus molecular subtypes (CMS) have emerged as a novel classification in colorectal cancer (CRC). However, these subtypes, were mostly derived from a US/European population, and have scant data in other ethnic groups. This study aimed to demonstrate molecular subtypes of CRC across geographic regions. Methods: Formalin fixed paraffin embedded (FFPE) tissue from untreated patients with stage II-III colon cancer from Brazil, Canada, Mexico, Thailand, and the US were evaluated. Gene expression profiling was performed at the University of Texas MD Anderson Cancer Center using NanoString’s nCounter technology and an optimized classifier for FFPE. Results: A total of 366 samples were included in this study, evenly distributed between the 5 international sites. While the US population matched previously reported distributions, the distribution of CMS subtypes varied substantially by region (P < 0.0001). While CMS1 was still associated with right-sided tumors (P < 0.001) and deficient mismatch repair (dMMR) (P < 0.001), the prevalence varied between 8% in Brazil to 30% in Mexico. CMS2 was found vary from 14% in Mexico to 47% in Brazil. The metabolic CMS3 subtype was present in only 3% in Thailand, but as high as 19% in Brazil. CMS4 was confirmed to be associated with higher stage (P = 0.047), and the prevalence was lowest in Brazil (14%) compared to 44% and 49% in US and Mexico, respectively. Expansion of study cohort is ongoing. Conclusions: CMS subtype prevalence differs substantially by geographic region in CRC. These variations suggest that transcriptomic-defined disease biology in international populations may be more heterogeneous than previously appreciated. Further studies in global populations are required to validate and extend these findings, which may have important impact for novel therapeutic development.