Rev Med UAS
Vol. 12: No. 2. Abril-Junio 2022
ISSN 2007-8013

Inestabilidad de Microsatélites como marcador biológico para la administración de Pembrolizumab

Microsatellites instability as a biological marker for the administration of Pembrolizumab

Fernández-Galindo Martha Alejandra1, Moreno-Ortiz José Miguel1, Contreras-Gutiérrez José Alfredo2, Martínez-Félix Jesús Israel3, Misael Guerrero-Valdez4, Beltrán-Ontiveros Saúl Armando2*.

  1. Instituto de Genética Humana “Dr. Enrique Corona Rivera”. Doctorado en Genética Humana. Departamento de Biología Molecular y Genómica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara. Guadalajara, Jalisco, México.
  2. Coordinación de Investigación, Centro de Investigación y Docencia en Ciencias de la Salud.
  3. Médico Adscrito al servicio de anestesiología, Centro de Investigación y Docencia en Ciencias de la Salud-Hospital Civil de Culiacán.
  4. Médico Adscrito al servicio de Ginecología y Obstetricia, Centro de Investigación y Docencia en Ciencias de la Salud-Hospital Civil de Culiacán.

*Autor de correspondencia: Dr. Saúl Armando Beltrán-Ontiveros
Coordinación de investigación del Centro de Investigación y Docencia en Ciencias de la Salud. UAS
Dirección: Eustaquio Buelna 91, Col. Burócrata, Código Postal: 80030 Culiacán Rosales, Sinaloa. México.
Teléfono: 667 3068465 saul.beltran@uas.edu.mx

DOI http://dx.doi.org/10.28960/revmeduas.2007-8013.v12.n2.008

Texto Completo PDF

Recibido 16 de enero 2022, aceptado 26 de marzo 2022

RESUMEN
Los microsatélites son secuencias cortas de ADN repetidas en tándem, distribuidas dentro del genoma, los cuales son propensos a errores en la replicación. El sistema Mismatch Repair (MMR), se encarga de identificar, señalar y reparar bases mal emparejadas, principalmente en secuencias repetitivas de ADN. La inactivación de cualquiera de los genes que codifican para las proteínas MMR puede provocar cambios en la longitud de los microsatélites causando un fenotipo hipermutable conocido como inestabilidad de microsatélites (MSI), vía de tumorigénesis bien establecida relacionada con la aparición, progresión y pronóstico de diversas neoplasias malignas. Debido a la gran cantidad de mutaciones somáticas, los tumores MSI tienen mayor sensibilidad a la inmunoterapia. La FDA ha aprobado un anticuerpo monoclonal como tratamiento para pacientes pediátricos y adultos con tumores sólidos MSI, el cual ha demostrado una actividad antitumoral sólida y duradera y un perfil de seguridad manejable contra varias neoplasias malignas avanzadas.
Palabras clave: Microsatélites, marcador biológico, Pembrolizumab

ABSTRACT
Microsatellites are short tandem repeating DNA sequences, distributed within the genome, that are prone to replication errors. The mismatch repair system (MMR) is responsible for identifying, signaling, and repairing mismatched bases, primarily in repetitive DNA sequences. Inactivation of any of the genes that encode MMR proteins can cause changes in the length of the microsatellites, and like a consequence a hypermutable phenotype known as microsatellite instability (MSI), a wellestablished tumorigenesis pathway related to the appearance, progression, and prognosis of various malignant neoplasms. Due to the large number of somatic mutations, MSI tumors are more sensitive to immunotherapy. The FDA has approved a monoclonal antibody as a treatment for pediatric and adult patients with MSI solid tumors, which has demonstrated robust and long-lasting antitumor activity and a manageable safety profile against various advanced malignancies.
Keywords: Microsatellites, biological marker, Pembrolizumab

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