Rojas-Jiménez, ErnestoMejía-Gómez, Javier CésarDíaz-Velásquez, ClaraQuezada-Urban, RosalíaMartínez Gregorio, HéctorVallejo-Lecuona, Fernandode la Cruz-Montoya, AldoPorras Reyes, Fany IrisPérez-Sánchez, Víctor ManuelMaldonado-Martínez, Héctor AquilesRobles-Estrada, MaybellineBargalló-Rocha, EnriqueCabrera-Galeana, PaulaRamos-Ramírez, MaritzaChirino, Yolanda IrasemaAlonso Herrera, LuisTerrazas, Luis IgnacioOliver, JavierFrecha, CeciliaPerdomo, SandraVaca-Paniagua, Felipe2022-07-072022-07-072020-11-19Rojas-Jiménez E, Mejía-Gómez JC, Díaz-Velásquez C, Quezada-Urban R, Martínez Gregorio H, Vallejo-Lecuona F, et al. Comprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic. Genes. 2020 Nov 19;11(11):1367http://hdl.handle.net/10668/3757Triple-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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Triple-negative breast cancerWhole exome sequencingWESTreatmentSomatic mutationMutational signaturesNeoplasias de la mama triple negativasSecuenciación del exoma completoTerapéuticaNeoplasias de la mamaMéxicoMedical Subject Headings::Persons::Persons::Age Groups::AdultMedical Subject Headings::Persons::Persons::Age Groups::Adult::AgedMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::DNA Repair-Deficiency DisordersMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Kaplan-Meier EstimateMedical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocytes, Tumor-InfiltratingMedical Subject Headings::Persons::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNAMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast NeoplasmsMedical Subject Headings::Geographical Locations::Geographic Locations::Americas::North America::Mexicoresearch article33227964open access10.3390/genes111113672073-4425PMC7699204