Abstract 206: The Consensus Molecular Classification (CMS) of primary colorectal tumors and their matched liver metastasis: Investigating the concordance
Authors: Vecchione Loredana , Beumer Ines , Snel Mireille , Salazar Ramon , Pietrantonio Filippo , Loupakis Fotios , Vivas Cristina Santos , Martinez-Villacampa Maria Mercedes , Sanjuan Xavier , Martinetti Antonia , Fuca' Giovanni , Schirripa Marta , Fassan Matteo , Bernards Rene' 
Published: August 2018

Background The Consensus Molecular Subtypes (CMS) identified four different molecular groups in colorectal cancer (1). Coding mutations are concordant between primary tumors (PT) and matched metastasis (MM) while gene copy numbers seem highly discordant (2). This could somehow influence the molecular classification of PT and MM. We therefore aimed to investigate the concordance of the CMS between PT and MM.

Material and methods We retrospectively collected 25 fresh matched samples of primary (P) and synchronous liver metastasis (LM) (discovery cohort) and 50 formalin-fixed-paraffin embedded (FFPE) samples of P and synchronous LM (validation cohort) of chemonaive metastatic colorectal cancer patients. All samples contained at least 30% of tumor cells. RNA was extracted from four sections of 5-μm by using the RNeasy FFPE kit (Qiagen). RNA yield was quantified using a NanoDrop spectrophotometer. Extracted RNA was amplified using a TransPLEX C-WTA whole-transcriptome amplification kit. Amplified cDNA was labeled using the Genomic DNA Enzymatic Labeling Kit and hybridized onto Agendia's full genome arrays both according to the manufacturer's instructions. For FFPE samples, no reference channel was used. Gene expression intensities were normalized using Lowess normalization method implemented in Matlab software version R2012a, and the CMS classification was applied as in Guinney et al (1).

Results and conclusion Clinical data were currently available for 66% of patients. Median age at the diagnosis was 64 (35-76), 30% of patients were female and 70% were male. 42% of PT were right side located and 58% were left side located. 42% of tumors were well differentiated, 40% moderately differentiated, 15% poorly differentiated and 3% were not classified. 3% of tumors were MSI, 45% were MSS. No data on the MMR status was available (NA) for 52% of the tumors. Mutations in KRAS were detected in 18% of the tumors while 30% were wild type (WT) and 52% NA. BRAF(V600E) mutation was detected in 3% of tumors, 39% were WT and 58 NA. 73% of patients received surgery of both P and LM simultaneously and before starting a systemic treatment. 72% of patients received a first line treatment. The results of the molecular classification will be presented at the conference.

References 1. Guinney J et al. The consensus molecular subtypes of colorectal cancer Nat Med. 2015 Nov;21(11):1350-62. 2.Mamlouk S et al. DNA copy number changes define spatial patterns of heterogeneity in colorectal cancer. Nat Commun. 2017 Jan 25;8:14093

Citation Format: Loredana Vecchione, Ines Beumer, Mireille Snel, Ramon Salazar, Filippo Pietrantonio, Fotios Loupakis, Cristina Santos Vivas, Maria Mercedes Martinez-Villacampa, Xavier Sanjuan, Antonia Martinetti, Giovanni Fuca', Marta Schirripa, Matteo Fassan, Rene' Bernards. The Consensus Molecular Classification (CMS) of primary colorectal tumors and their matched liver metastasis: Investigating the concordance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 206.