Portal de investigación
Comprehensive genomic profile of heterogeneous long follow-up triple-negative breast cancer and its clinical characteristics shows DNA repair deficiency has better prognostic
Fecha de publicación:
Fecha Ahead of Print:
Autores organización
Autores
- Rojas-Jiménez E
- Mejía-Gómez JC
- Díaz-Velásquez C
- Quezada-Urban R
- Gregorio H.M.
- Vallejo-Lecuona F
- de la Cruz-Montoya A
- Reyes F.I.P.
- Pérez-Sánchez VM
- Maldonado-Martínez HA
- Robles-Estrada M
- Bargalló-Rocha E
- Cabrera-Galeana P
- Ramos-Ramírez M
- Chirino YI
- Herrera L.A.
- Terrazas LI
- Oliver J
- Frecha C
- Vaca-Paniagua F
Grupos de investigación
Resumen
Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Datos de la publicación
- ISSN/ISSNe:
- 2073-4425, 2073-4425
- Tipo:
- Article
- Páginas:
- 1-21
- Enlace a otro recurso:
- www.scopus.com
Genes MDPI AG
Citas Recibidas en Web of Science: 3
Citas Recibidas en Scopus: 6
Documentos
- No hay documentos
Filiaciones
Keywords
- Adult; Aged; DNA Repair-Deficiency Disorders; Female; Humans; Kaplan-Meier Estimate; Lymphocytes, Tumor-Infiltrating; Middle Aged; Mutation; Triple Negative Breast Neoplasms; Whole Exome Sequencing; platinum complex; adult; aged; Article; cancer prognosis; CDKN1B gene; clinical article; controlled study; disease free survival; DNA repair; female; follow up; gene mutation; genetic analysis; genetic variability; histopathology; human; immunohistochemistry; male; oncogene; overall survival; PIK3CA gene; PTEN gene; staining; TP53 gene; treatment response; triple negative breast cancer; tumor associated leukocyte; tumor suppressor gene; whole exome sequencing; disorders of DNA synthesis and repair; genetics; Kaplan Meier method; middle aged; mortality; mutation; pathology; triple negative breast cancer
Proyectos asociados
Desarrollo de un producto antimicrobiano con base en propóleos para uso odontológico en Endodoncia. Fase I estudios Fitoquímicos, Citotóxicos y Antimicrobianos.
Investigador Principal: YORMARIS CASTILLO ROMERO
PCI-2018-10160 . 2019
Determinación de la huella transcipcional de mastocitos aislados de pulpa dental humana sana y con signos clínicos de inflamación
Investigador Principal: MARIA ROSA BUENAHORA TOBAR
PCI-2019-10765 . 2020
Prototipo de un dispositivo analítico tridimensional basado en papel para la detección colorimétrica del virus del papiloma humano en puntos de atención
Investigador Principal: SANDRA JANNETH PERDOMO LARA
PCI-2019-10777 . 2020
Desarrollo de un modelo de epitelio asociado a folículo ( FAE ) en ambiente HLA-B27 positivo: una aproximación para en estudio in vitro de transcitosis reversa de SIgA en las espondiloartritis
Investigador Principal: JULIETTE DE AVILA QUIROGA
UEB-2019-517 . 2019
Desarrollo de un sistema de hipertermia a frecuencia de microondas para el tratamiento de cáncer de mama con monitoreo de temperatura
Investigador Principal: HECTOR FABIAN GUARNIZO MENDEZ
UEB-2019-524 . 2019
Citar la publicación
Rojas E,Mejía JC,Díaz C,Quezada R,Gregorio HM,Vallejo F,de la Cruz A,Reyes FIP,Pérez VM,Maldonado HA,Robles M,Bargalló E,Cabrera P,Ramos M,Chirino YI,Herrera LA,Terrazas LI,Oliver J,Frecha C,Perdomo S,Vaca F. Comprehensive genomic profile of heterogeneous long follow-up triple-negative breast cancer and its clinical characteristics shows DNA repair deficiency has better prognostic. Genes (Basel). 2020. 11. (11):p. 1-21. IF:4,096. (2).