Differential clinicopathological and molecular features within late-onset colorectal cancer according to tumor location

// Lorena Brandariz 1 , María Arriba 2 , Juan Luis García 3, 4 , Juana María Cano 5 , Daniel Rueda 6, 7 , Eduardo Rubio 8 , Yolanda Rodríguez 9 , Jessica Pérez 3, 4 , Alfredo Vivas 8 , Carmen Sánchez 8 , Sandra Tapial 7 , Laura Pena 10 , Mariano García-Arranz 11 , Damián García-Olmo 1, 11 , Miguel Urioste 10, 12 , Rogelio González-Sarmiento 3, 4 and José Perea 1, 11 1 Surgery Department, Fundación Jiménez Díaz University Hospital, Madrid, Spain 2 Biochemistry Department, Gregorio Marañón University Hospital, Madrid, Spain 3 Molecular Medicine Unit, Department of Medicine, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain 4 Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-SACYL-CSIC, Salamanca, Spain 5 Oncology Department, Ciudad Real General Hospital, Ciudad Real, Spain 6 Molecular Biology Laboratory, “12 de Octubre” Universitary Hospital, Madrid, Spain 7 Digestive Cancer Research Group, “12 de Octubre” Research Institute, Madrid, Spain 8 Surgery Department, “12 de Octubre” Universitary Hospital, Madrid, Spain 9 Pathology Department, “12 de Octubre” Universitary Hospital, Madrid, Spain 10 Familial Cancer Clinical Unit, Spanish National Cancer Centre (CNIO), Madrid, Spain 11 Health Research Institute, Fundación Jiménez Díaz University Hospital, Madrid, Spain 12 Centre for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, Madrid, Spain Correspondence to: José Perea, email: josepereag@hotmail.com Keywords: late-onset colorectal cancer; microsatellite instability; chromosomal instability; CpG island methylator phenotype; colon location Received: November 27, 2017 Accepted: February 10, 2018 Epub: February 15, 2018 Published: March 16, 2018 ABSTRACT Background: Since there is a predilection of some clinical and molecular features for a given tumor location, we assessed whether this can be confirmed in late-onset colorectal cancer (LOCRC). Results: Right colon cancers showed features associated with sporadic Microsatellite Instability: predominance of female cases and BRAF mutations, and an important mucinous component. Left colon cancers developed a higher number of polyps and multiple primary CRCs, showed the strongest familial component, and had better prognosis. Rectal cancers showed a predominantly sporadic phenotype, with worse prognosis and a CpG Island Methylator Phenotype (CIMP)-High. No copy number alterations (CNAs) greater than or equal to 50% were observed in this LOCRC group, and the most recurrent alterations were losses at 5q13 and 14q11, and gains at 7q11, 7q21-q22, 19p13-p12, 19q13 and 20p11-q11. KRAS and PIK3CA were the only mutated genes showing differences according to the tumor location, mainly for right colon cancers. Materials and Methods: We analyzed clinical and molecular characteristics of LOCRC at different tumor locations in order to determine if there are differential phenotypes related with the location in the colon. Conclusions: Categorizing LOCRC according to tumor location appears to be an adequate first step to resolving the heterogeneity of this subset of CRC.