Caracterización de pacientes con cáncer colorrectal esporádico basado en la nueva subclasificación molecular de consenso

Abstract

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 (Rev Med Chile 2017; 145: 419-430)

Prevalence of the Braf P.V600E Variant in Patients with Colorectal Cancer from Mexico and Its Estimated Frequency in Latin American and Caribbean Populations

“…Colomba et al , 16 Lopez-Rios et al 18 and Jurkowska et al 19 suggested that differences in methodologies could alter p.V600E frequencies, principally for patients with melanoma, but it was also for patients with CRC, as described by Løes et al 20 and Roma et al . 17 However, the discrepancy between variant frequencies reported by Wielandt et al 15 and the present study is still unclear since detection of the variant allele was performed by Sanger sequencing in both studies. In fact, this approach was used in 56% of the selected studies in Latin America and the Caribbean.…”

“…From the 17 selected reports, the estimated frequency ranged from 0% to 15% with sample sizes ranging from 36 to 120 patients. By comparing the selected populations, we only identified a significant difference in the frequency of BRAF p.V600E with one of the four Chilean populations included, the study of Wielandt et al , 15 with statistical significance (p=0.02). It must be noted that these authors described 53 patients who showed the highest variant frequency (15%) among the selected studies, with a median age of 70 years.…”

“…Rubí-Castellanos et al 26 outlined the ancestry of Western Mexicans, showing that 53.2% are of Native American, 30.8% of European and 15.9% of African descent. Moreover, Santiago City in Chile, where the Wielandt et al 15 study population originated from, is within the central zone of Chile characterized by Eyheramendy et al ,27 with 40.43% Native American ancestry, 2.46% African and 57.11% European ancestry, which is the highest percentage among Chilean populations. The genetic descent of patients with CRC from Western Mexico and Central Chile might be a crucial factor in producing the differences in frequency of BRAF p. V600E, which is further supported by the statistical discrepancy in the comparison of the whole variant frequency of 10.7%, considering the conclusive results for 28 of the 261 Central Chilean patients with CRC analyzed,15 28–30 in contrast to the 4% frequency estimated for Western Mexican patients with CRC (p=0.04).…”

Diagnosis of molecular subtypes of colorectal cancer using immunohistochemistry

“…Таким образом, гиперметилирование промотора генасупрессора опухоли приводит к подавлению транскрипции и может явиться решающим этапом в онкогенезе. CIMP-положительные опухоли часто связаны с BRAF или KRAS мутациями, но имеют низкую частоту мутаций TP53 [10][11][12].…”

Situación actual del cáncer de colon en Chile: una mirada traslacional

“…Respecto de los daños genómicos que ocurren en el desarrollo del CCR, se describen las siguientes rutas: (i) la inestabilidad cromosómica (CIN) donde cambia el número y la estructura del cromosoma, afectando la función de genes represores de tumores, o aumentando el número de copias de protooncogenes; (ii) la inestabilidad microsatelital (MSI) donde la célula es incapaz de corregir deleciones o inserciones en regiones repetitivas del ADN generando un amplio número de mutaciones y (iii) el fenotipo metilador (CIMP) en el cual los promotores de genes supresores de tumores están hipermetilados y, por lo tanto, inactivos. Se ha mostrado que el 50% de los pacientes chilenos tienen alta CIN 23 , entre el 17% al 27% tiene alta MSI 19,21,23 y por último un 31% tiene alto grado de CIMP 23 .…”