ARTÍCULO DE INVESTIGACIÓN - Caracterización de pacientes con cáncercolorrectal esporádico basado en lanueva subclasificación molecular deconsenso

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ARTÍCULO DE INVESTIGACIÓN 419 Rev Med Chile 2017; 145: 419-430 Caracterización de pacientes con cáncer colorrectal esporádico basado en la nueva subclasificación molecular de consenso Ana María Wielandt1,a, Cynthia Villarroel1,a, Claudia Hurtado1,b, Daniela Simian2,c, Diego Zamorano4, Maripaz Martínez2,c, Magdalena Castro2,d, María Teresa Vial3, Udo Kronberg4, Francisco López-Kostner4 Characterization of patients with sporadic colorectal cancer following the new Consensus Molecular Subtypes (CMS) Background: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. Aim: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways. Material and Methods: Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal. Results: CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases. Conclusions: This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine. (Rev Med Chile 2017; 145: 419-430) Key words: Carcinogenesis; Chromosomal Instability; Colorectal Neoplasms; CpG Island; Microsatellite Instability. 1Laboratorio de Oncología y Genética Molecular, Clínica Las Condes, Santiago, Chile. 2Dirección Académica, Clínica Las Condes, Santiago, Chile. 3Unidad de Anatomía Patológica, Clínica Las Condes, Santiago, Chile. 4Unidad de Coloproctología, Clínica Las Condes, Santiago, Chile. aBioquímico. bPhD en Ciencias. cEnfermera Universitaria. dEnfermera Universitaria MSC en Epidemiología. Fuente de apoyo financiero: Proyecto Fondecyt 1140012. Recibido el 30 de diciembre de 2016, aceptado el 25 abril de 2017. Correspondencia a: Ana María Wielandt N. Lo Fontecilla 441, Las Condes, Santiago, Chile. awielandt@clc.cl El cáncer colorrectal (CCR) representa un importante problema de salud a nivel mundial, ocupando el tercer lugar entre los cánceres más frecuentes y el cuarto en mortalidad por cáncer1,2. En Chile, se ha duplicado su mortalidad en los últimos años a pesar de los programas de prevención primaria, ocupando el cuarto lugar de muerte por cáncer en hombres y el quinto en mujeres3. En los últimos años, el modelo para CCR


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