Comprehensive clinical, pathological and molecular characterization of a cohort of locally advanced rectal cancer patients: Towards an integrative classification for rectal cancer management

O. PODHAJCER; R. SALANOVA; M KUJARUK; M. CORAGLIO; J. SENDOYA; A. LLERA; E. FERNANDEZ; M. RIZZOLO; A. CABANNE; E. ROCA; M. GOLUBICKI; C. ROTONDARO; V. MIKOLAITIS; U. GUALDRINI; S. ISEAS

Congreso; Reunión Conjunta Anual de Sociedades de Biociencias. Buenos Aires; 2017

Introduction: Locally AdvancedRectal Cancer (LARC) response to preoperative chemoradiotherapy (CRT) is veryheterogeneous. Current prognosis-related factors lack robustness toindividualize therapeutic decisions. Four Consensus Molecular Subtypes (CMS)represent the current best description of colorectal cancer heterogeneity atthe gene expression level. We aim to integrate CMS predictions with available clinicaldata from an Argentinian LARC cohort in search of biomarkers to improve patientmanagement. Methods: We analyzedgene expression in baseline tumor biopsies of the first 24 LARC patients from anongoing recruiting translational research trial. Mutations in RAS and BRAF weremeasured by PCR Entrogen panel. DNA repair proteins(MLH1,MSH2,MSH6,PMS2) weremeasured by Cell Marque monoclonal primary antibodies. Gene expression data wasobtained using Agilent Agi4x44K Whole Human Genome microarrays, andCMS-classified with the R package ?CMSclassifier? using asimilarity-to-centroid approach. Results:Subtype classification showed CMS2-Canonical subtype patients (79%) ofwhich one showed MSH2 gene and protein expression deficit, and one carried KRASG12A mutation; CMS3-Metabolic (13%) with one KRAS-mut patient; CMS1-MSI immune(4%) diagnosed Lynch Syndrome confirmed by a germinal MSH2 mutation;CMS4-Mesenchymal (4%) showing higher stromal gene expression. Conclusion: To our knowledge, this isthe first classification of local LARC patients into descripted colorectal molecularsubtypes combining prospective clinical and genomic data to enrich patientcharacterization. We expect that future analyzed cases from this ongoing trialmight help us establish further molecular features to correlate with CRT response.