Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/18156
Título
Comprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic
Autor(es)
Rojas-Jiménez, Ernesto | Mejía-Gómez, Javier César | Díaz-Velásquez, Clara | Quezada-Urban, Rosalía | Martínez Gregorio, Héctor | Vallejo-Lecuona, Fernando | de la Cruz-Montoya, Aldo | Porras Reyes, Fany Iris | Pérez-Sánchez, Víctor Manuel | Maldonado-Martínez, Héctor Aquiles | Robles-Estrada, Maybelline | Bargalló-Rocha, Enrique | Cabrera-Galeana, Paula | Ramos-Ramírez, Maritza | Chirino, Yolanda Irasema | Alonso Herrera, Luis | Terrazas, Luis Ignacio | Oliver, Javier | Frecha, Cecilia | Perdomo, Sandra ISCIII | Vaca-Paniagua, Felipe
Fecha de publicación
2020-11-19
Idioma
Inglés
Tipo de documento
research article
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.
Palabras clave
Triple-negative breast cancer | Whole exome sequencing | WES | Treatment | Somatic mutation | Mutational signatures | Neoplasias de la mama triple negativas | Secuenciación del exoma completo | Terapéutica | Neoplasias de la mama | México
MESH
Adult | Aged | DNA Repair-Deficiency Disorders | Female | Humans | Kaplan-Meier Estimate | Lymphocytes, Tumor-Infiltrating | Middle Aged | Breast Neoplasms | Sequence Analysis, DNA | Mutation | Triple Negative Breast Neoplasms | Mexico
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