RESUMO
CONTEXT: The fusion gene BCR-ABL1 is present in at least the fourth part of B-cell acute lymphoblastic leukemia adult cases. Patients with this fusion gene are candidates to tyrosine kinase inhibitors treatment, and the response to this therapy can be measure by quantification of BCR-ABL1 transcripts. Some patients relapse because the presence of mutations in the tyrosine kinase domain of BCR-ABL1. CASE REPORT: This is a report of a patient with BCR-ABL1 who initially achieved molecular response with imatinib therapy, relapsing after fifteen months. The treatment was changed to dasatinib, but the patient doesn't achieve molecular response. Retrospectively, we analyzed the tyrosine kinase domain of BCR-ABL1 and we found three mutations (E459K, E255K and V299L). CONCLUSIONS: We conclude that gain of mutations during treatment with TKIs has strong impact in the progress of disease, being relevant the detection of BCR-ABL1 mutations in relapsed patients or in case of BCR-ABL1 persistence.
Assuntos
Biomarcadores Tumorais/genética , Proteínas de Fusão bcr-abl/genética , Mutação/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adulto , Feminino , Humanos , PeruRESUMO
OBJECTIVE: To determine the presence of microsatellite instability in patients with colorectal cancer using the molecular panel Bethesda and discuss its significance in patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome. MATERIALS AND METHODS: We worked with samples of peripheral blood and tumor tissue of 28 patients diagnosed with colorectal cancer referred to the Laboratory of Molecular Biology of the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, with suspected of Lynch syndrome. DNA was extracted using kits of nucleic acid extraction of peripheral blood and paraffin-embedded tumor tissue. Five microsatellite markers of Bethesda panel were amplified: BAT25, BAT26, D2S123, D5S346 and D17S250, by polymerase chain reaction. IMS analysis was performed by electrophoresis on chip in the Bioanalyzer Agilent 2100. RESULTS: Of the patients studied, 11 had high IMS(IMS-H) and one could not be fully ranked, staying as MSI-H / IMS-L. In all cases of IMS-H both BAT26 and BAT25 were unstable. The IMS-H in these patients indicates high probability of HNPCC or Lynch syndrome; it must be contrasted with the genetic analysis of MMR genes. CONCLUSION: The technique allowed determine which patients have to continue with the study of system mismatch repair genes, for establish whether we facing to HNPCC or sporadic colorectal cancer.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Instabilidade de Microssatélites , Adulto , Idoso , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
Determinar la presencia de inestabilidad de microsatélites en pacientes con cáncer colorrectal usando el panel molecular Bethesda y discutir su importancia en pacientes con sospecha de cáncer colorrectal hereditario no polipósico (HNPCC) o con sospecha de síndrome de Lynch. Materiales y métodos: Se trabajó con muestras de sangre periférica y tejido tumoral de 28 pacientes con diagnóstico de cáncer colorrectal remitidos al laboratorio de Biología Molecular del Instituto Nacional de Enfermedades Neoplásicas (INEN) de Lima, bajo sospecha de Síndrome de Lynch. El ADN fue extraído utilizando kits de extracción de ácidos nucleicos para sangre periférica y tejido tumoral embebido en parafina. Se amplificaron los cinco marcadores microsatélites del panel Bethesda: BAT25, BAT26, D2S123, D5S346 y D17S250, por reacción en cadena de la polimerasa. El análisis de IMS fue realizado mediante electroforesis en chip en el bioanalizador Agilent 2100. Resultados: Del total de pacientes estudiados 11 tuvieron IMS alta (IMS-H) y uno no pudo ser totalmente clasificado quedando como IMS-H/IMS-L. En todos los casos de IMS-H tanto BAT25 como BAT26 resultaron inestables. La IMS-H en estos pacientes indica mayor probabilidad de HNPCC o síndrome de Lynch, lo cual debe ser contrastado con el análisis genético de los genes MMR. Conclusión: La técnica permitió determinar cuáles son los pacientes que deben continuar con el estudio de los genes del sistema de reparación de mal apareamiento del ADN, para establecer si estamos frente a casos de HNPCC o ante casos de cáncer colorrectal esporádicos...
To determine the presence of microsatellite instability in patients with colorectal cancer using the molecular panel Bethesda and discuss its significance in patients with suspected hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome. Materials and methods: We worked with samples of peripheral blood and tumor tissue of 28 patients diagnosed with colorectal cancer referred to the Laboratory of Molecular Biology of the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, with suspected of Lynch syndrome. DNA was extracted using kits of nucleic acid extraction of peripheral blood and paraffin-embedded tumor tissue. Five microsatellite markers of Bethesda panel were amplified: BAT25, BAT26, D2S123, D5S346 and D17S250, by polymerase chain reaction. IMS analysis was performed by electrophoresis on chip in the Bioanalyzer Agilent 2100. Results: Of the patients studied, 11 had high IMS (IMS-H) and one could not be fully ranked, staying as MSI-H / IMS-L. In all cases of IMS-H both BAT26 and BAT25 were unstable. The IMS-H in these patients indicates high probability of HNPCC or Lynch syndrome; it must be contrasted with the genetic analysis of MMR genes. Conclusion: The technique allowed determine which patients have to continue with the study of system mismatch repair genes, for establish whether we facing to HNPCC or sporadic colorectal cancer...
Assuntos
Humanos , Instabilidade de Microssatélites , Neoplasias Colorretais Hereditárias sem Polipose , Reação em Cadeia da PolimeraseRESUMO
En la Leucemia linfática aguda (LLA) pediátrica las cinco fusiones génicas más frecuentes descritas son: ETV6/RUNX1, BCR/ABL variante p190, BCR/ABL variante p210, E2A/PBX1, MLL/AF4 y representan alrededor del 40%. Se busca determinar la frecuencia e importancia de las principales fusiones génica en la leucemia linfática en un grupo de pacientes pediátricos del INEN. Se realizó el análisis molecular de cinco genes de fusión en 23 pacientes con diagnóstico de LLA-B, obteniéndose las siguientes frecuencias: ETV6/RUNX1 (17.4%), BCR/ABL variante p190 (8.7%), BCR/ABL variante p210 (8.7%), E2A/PBX1 (8.7%), MLL/AF4 (4.3%). Esta metodología de estudio de los cinco genes de fusión, debe considerarse como herramienta de apoyo al diagnóstico y monitoreo en uso de terapias blanco en todos los casos de la LLA-B pediátricas.
