RESUMEN
Objective To describe the frequency of mutations in DNA-repair genes in a southwestern Colombian population. Methods We have designed an observational study, including 162 people from all ages from southwest Colombia. We have extracted and collected their DNA in filters. We have immersed the DNA in a phosphate buffer along with DNeasy package (Thermo Fisher Scientific, Waltham, MA, USA). The preparation process was with the TruSeq Exome Library Prep (Illumina, Inc. San Diego, CA, USA), then the obtained libraries were normalized with TruSeq Rapid Exome (Illumina, Inc. San Diego, CA, USA). We sequenced the full exome and identified the variants associated with 12 genes (ataxia telangiectasia mutated [ATM], BRCA1 DNA repair associated [BRCA1], BRCA2 DNA repair associated [BRCA2], checkpoint kinase 2 [CHEK2], epithelial cell adhesion molecule [EPCAM], homeobox protein Hox-B13 [HOXB13], mutS homolog 1, 2 and 6 [MLH1, MSH2, MSH6], nibrin [NBN], PMS1 homolog 2, mismatch repair system component [PMS2], and tumor protein p53 [TP53]). Descriptive statistics were performed with the R software (The R Foundation for Statistical Computing, Vienna, Austria). Results A total of 7,315,466 pieces of data were sequenced in this population. The most frequently mutated genes were ATM (1,221 pieces of data; 13.2%), BRCA1 (1,178 pieces of data; 12.8%), BRCA2 (1,484 pieces of data; 16.12%), and NBN (965 pieces of data; 10.42%). The most common single nucleotide polymorphisms (SNPs) in these 12 genes were the following: BRCA2 (rs169547, rs206075, rs206076); ATM (rs659243, rs228589); TP53 (rs1625895, rs1042522, rs1642785); PMS2 (rs2228006, rs1805319); NBN (rs709816); and MSH6 (rs3136367) Conclusion The BRCA2, ATM, BRCA1 and NBN DNA-repair genes were the most frequently mutated in this southwestern Colombian Population
Objetivo Describir la frecuencia de las mutaciones en los genes de reparación del ADN en una población del suroccidente de Colombia. Métodos Diseñamos un estudio observacional que incluyó a 162 personas del suroccidente de Colombia de todas las edades. Hemos extraído y recogido el ADN en filtros. Los sumergimos en tampón fosfato junto con el paquete DNeasy (Thermo Fisher Scientific, Waltham, MA, EEUU). El proceso de preparación fue realizado con TruSeq Exome Library Prep (Illumina, Inc. San Diego, CA, EEUU); luego, las bibliotecas obtenidas se normalizaron con TruSeq Rapid Exome (Illumina, Inc. San Diego, CA, USA). Secuenciamos el exoma completo e identificamos las variantes asociadas a doce genes (ataxia telangiectasia mutated [ATM], BRCA1 DNA repair associated [BRCA1], BRCA2 DNA repair associated [BRCA2], checkpoint kinase 2 [CHEK2], epithelial cell adhesion molecule [EPCAM], homeobox protein Hox-B13 [HOXB13], mutS homolog 1, 2 and 6 [MLH1, MSH2, MSH6], nibrin [NBN], PMS1 homolog 2, mismatch repair system component [PMS2], y tumor protein p53 [TP53]). La estadística descriptiva se realizó en el programa R (The R Foundation for Statistical Computing, Viena, Austria). Resultados Un total de 7.315.466 datos fueron secuenciados en esta población. Los genes más frecuentemente mutados fueron el ATM, con 1.221 datos (13,2%), el BRCA1, con 1.178 datos (12,8%), el BRCA2, con 1.484 datos (16,12%) y el NBN, con 965 datos (10,42%). Los polimorfismos de un solo nucleótido (PSN) más comunes en estos 12 genes fueron los siguientes: BRCA2 (rs169547, rs206075, rs206076); ATM (rs659243, rs228589); TP53 (rs1625895, rs1042522, rs1642785); PMS2 (rs2228006, rs1805319); NBN (rs709816) y MSH6 (rs3136367) Conclusión Los genes de reparación de ADN BRCA2, ATM, BRCA1 NBN fueron los más frecuentemente mutados en esta población del suroccidente de Colombia.