RESUMEN
OBJECTIVES: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer. METHODS: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy. RESULTS: From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months. CONCLUSION: We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Genómica/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Análisis de Secuencia de ADN/métodos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Genómica/tendencias , Estimación de Kaplan-Meier , Terapia Molecular Dirigida/métodos , Metástasis de la Neoplasia , Neoplasias/mortalidad , Neoplasias/patología , Medicina de Precisión/métodos , Receptor ErbB-2/antagonistas & inhibidores , Reproducibilidad de los Resultados , Análisis de Secuencia de ADN/tendencias , Factores de Tiempo , Resultado del TratamientoRESUMEN
Background: Acute myeloid leukemia [AML] is a heterogeneous clonal disorder in terms of cytogenetic and molecular aberrations. Ten-Eleven-Translocation 2 [TET2], Kirsten rat sarcoma viral oncogene homolog [KRAS], and Casitas B-cell lymphoma [CBL] have an important role pathogenesis of acute myeloid leukemia [AML] and their activated mutations confer proliferative and survival signals
Aim: In this study, we aimed to find possible genetic markers for molecular analysis in childhood AML by screening hot-spot exons of TET2, KRAS, and CBL using Next Generation Sequencing [NGS] analysis. In addition, association between found variants and mutations of Januse Kinase-2 [JAK2] and Fms-Related Tyrosine Kinase [FLT3] were analyzed which are important prognostic risk factors for AML
Methods: Eight patients who were diagnosed with pediatric AML at Losante Pediatric Hematology- Oncology Hospital were included to the study. Hot-spot exons of TET2, KRAS and CBL genes were screened using the NGS method. Furthermore, FLT3-Internal Tandem Duplicate [FLT3-ITD] and JAK2-V617F were analyzed by Real Time Polymerase chain Reaction [Real Time-PCR]
Results: In total, we identified 20 variants in studied genes by NGS. In our patient group, 16 variants in the TET2 [seven novel, seven missense and two silent], two variants in the KRAS [one missense and one intronic] and two variants in the CBL [two novel] were found. All of AML patients were found negative for JAK V617 F. Three of the eight patients [37.5%] showed mutations of both FLT3-ITD and TET2, KRAS, CBL
Conclusion: We found novel mutations forTET2, KRAS, and CBL. The detected variants in this article seem to be the first screening results of genes studied by NGS in childhood AML patients. Our results also showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations
Asunto(s)
Niño , Preescolar , Femenino , Humanos , Masculino , Proteínas de Unión al ADN/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas c-cbl/genética , Tirosina Quinasa 3 Similar a fms/genética , Janus Quinasa 2/genética , Análisis de Secuencia de ADN/tendenciasRESUMEN
Species identification of biological samples is widely used in such fields as forensic science and food industry. A variety of accurate and reliable methods have been developed in recent years. The current review shows common target genes and screening criteria suitable for species identification, and described various DNA-based molecular biology methods about species identification. Additionally, it discusses the future development of species identification combined with real-time PCR and sequencing technologies.
Asunto(s)
Animales , Humanos , ADN/genética , Técnicas Genéticas/tendencias , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN/tendenciasAsunto(s)
Biología Molecular , Técnicas Genéticas/métodos , Técnicas Genéticas/tendencias , Análisis de Secuencia de ADN/tendencias , Análisis de Secuencia por Matrices de Oligonucleótidos/tendencias , Clonación Molecular/métodos , Enzimas de Restricción del ADN , ADN Recombinante , Predicción , Terapia Genética , Hibridación in Situ/tendencias , Nucleótidos/análisis , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/tendenciasRESUMEN
En este artículo se presenta un modelo de codificación de Redes Neuronales Artificiales basado en computación con ADN mediante el cual es posible diseñar una red que sea capaz de responder adecuadamente ante cualquier impulso en su entrada. Se hace uso de las operaciones de manipulación de cadenas genéticas que se emplean a nivel de laboratorio en la actualidad y trabajos previos en computación con ADN que permiten una futura implementación de ese esquema. Se propone también una técnica de aprendizaje nueva basada en los conceptos de selección natural que aprovecha la capacidad de cómputo masivamente paralelo inherente a la estructura biológica del ADN