Mutational profile by targeted next generation sequencing of non-small cell lung cancer in the Mexican population / Perfil mutacional por secuenciación de nueva generación en cáncer de pulmón de células no pequeñas en población mexicana

Abstract: Objective: Targeted next-generation sequencing (t-NGS) has revolutionized clinical diagnosis allowing multiplexed detection of genomic alterations. This study evaluated the profile of somatic mutations by t-NGS in Mexican patients with non-small cell lung cancer (NSCLC). Materials and methods: Genomic DNA was extracted from 90 lung adenocarcinomas and sequences were generated for a panel of 48 cancer genes. Epidermal Growth Factor Receptor (EGFR) mutations were detected in parallel by quantitative PCR. Results: The mutational profile of NSCLC revealed alterations in 27 genes, where TP53 (47.8%) and EGFR (36.7%) exhibited the highest mutation rates. EGFR Q787 mutations were present in 14 cases (15.6%), 10 cases had exon 19 deletions (11.1%), seven cases had L858R (7.8%). The mutational frequency for genes like EGFR, MET, HNF1A, HER2 and GUSB was different compared to caucasian population. Conclusion: t-NGS improved NSCLC treatments efficacy due to its sensitivity and specificity. A distinct pattern of somatic mutations was found in Mexican population.

Resumen: Objetivo: La secuenciación dirigida de nueva generación (SNG) permite la detección múltiple de mutaciones. Este estudio evalúa el perfil de mutaciones somáticas por SNG en pacientes mexicanos con cáncer de pulmón de células no pequeñas (CPCNP). Material y métodos: Se aisló ADN de 90 muestras de pacientes con CPCNP y se analizarón 48 genes relacionados con cáncer. Las mutaciones del receptor del factor de crecimiento epidérmico (EGFR) se detectaron por PCR cuantitativa. Resultados. Se detectaron alteraciones en 27 genes. Las mutaciones más frecuentes fueron TP53 (47.8%) y EGFR (36.7%). En el gen EGFR, 14 casos fueron mutaciones Q787 (15.6%), 10 presentaron microdeleciones en el exón 19 (11.1%), y siete en L858R (7.8%). La frecuencia de mutación en EGFR, MET, HNF1A, HER2 y GUSB fue diferente en comparación con población caucásica. Conclusión: NGS modifica el tratamiento del paciente con CPCNP por su sensibilidad y especificidad para detectar mutaciones. La población mexicana presenta un perfil mutacional particular.

Gene polymorphism of Helicobacter pylori correlates with its resistance to Clarithromycin / 中华消化内镜杂志

Objective To investigate the resistance rate of Helicobacter pylori (Hp) to clarithromycin and its correlation with point mutations in 23S rRNA gene. Methods Hp was cultured from gastric biopsy specimen obtained from 189 patients undergoing upper gastrointestinal endoscopy. The DNA of 11 clarithromycin sensitive Hp and 19 clarithromycin resistant Hp was extracted, and 23S rRNA was amplified and sequenced. Results The rate of clarithromycin resistance in cultured Hp was 29. 2%. Point mutations in 23S rRNA gene were found in 17 clarithromycin resistant Hp strains. The proportion of A to G mutation was 36.8%, G to A of 21.5%, C to T of 15.8%, A to C of 10.5% and T to C of 5.3%. No point mutation in 23S rRNA was detected in other 2 clarithromycin resistant and 11 sensitive Hp strains. Conclusion The resistance to clarithromycin is common in Hp, and point mutations in 23S rRNA gene of Hp are frequent in clarithromycin resistant strains, with most prevalent mutations of A to G and next G to A.