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Comprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic

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dc.contributor.authorRojas-Jiménez, Ernesto
dc.contributor.authorMejía-Gómez, Javier César
dc.contributor.authorDíaz-Velásquez, Clara
dc.contributor.authorQuezada-Urban, Rosalía
dc.contributor.authorMartínez Gregorio, Héctor
dc.contributor.authorVallejo-Lecuona, Fernando
dc.contributor.authorde la Cruz-Montoya, Aldo
dc.contributor.authorPorras Reyes, Fany Iris
dc.contributor.authorPérez-Sánchez, Víctor Manuel
dc.contributor.authorMaldonado-Martínez, Héctor Aquiles
dc.contributor.authorRobles-Estrada, Maybelline
dc.contributor.authorBargalló-Rocha, Enrique
dc.contributor.authorCabrera-Galeana, Paula
dc.contributor.authorRamos-Ramírez, Maritza
dc.contributor.authorChirino, Yolanda Irasema
dc.contributor.authorAlonso Herrera, Luis
dc.contributor.authorTerrazas, Luis Ignacio
dc.contributor.authorOliver, Javier
dc.contributor.authorFrecha, Cecilia
dc.contributor.authorPerdomo, Sandra
dc.contributor.authorVaca-Paniagua, Felipe
dc.contributor.authoraffiliation[Rojas-Jiménez,E; Díaz-Velásquez,C; Quezada-Urban,R; Martínez Gregorio,H; Vallejo-Lecuona,F; Terrazas,LI; Vaca-Paniagua,F] Laboratorio Nacional en Salud, Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-Degenerativas, Facultad de Estudios Superiores Iztacala, Tlalnepantla, Estado de México, Mexico. [Rojas-Jiménez,E; Quezada-Urban,R; Martínez Gregorio,H; Vallejo-Lecuona,F; de la Cruz-Montoya,A; Chirino,YI; Terrazas,LI; Vaca-Paniagua,F] Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, UNAM, Tlalnepantla, Estado de México, Mexico. [Mejía-Gómez,JC] Division of Breast Cancer, Department of Medical Oncology, Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Quezada-Urban,R] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. [Quezada-Urban,R] Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. [Porras Reyes,FI; Pérez-Sánchez,VM; Maldonado-Martínez,HA; Bargalló-Rocha,E; Cabrera-Galeana,P; Ramos-Ramírez,M; Alonso Herrera,L; Vaca-Paniagua,F] Instituto Nacional de Cancerología, CDMX, Mexico. [Robles-Estrada,M] Hospital General de Pachuca SSA, Pachuca, Mexico. [Alonso Herrera,L] Instituto Nacional de Medicina Genómica, CDMX, Mexico. [Alonso Herrera,L] Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas-Instituto Nacional de Cancerología, CDMX, Mexico. [Oliver,J] Medical Oncology Service, Hospitales Universitarios Regional y Virgen de la Victoria, Institute of Biomedical Research in Malaga, CIMES, University of Málaga, Málaga, Spain. [Frecha,C] Unidad de Producción Celular del Hospital Regional Universitario de Málaga—IBIMA—Málaga, Málaga, Spain. [Perdomo,S] Instituto de Nutrición, Genética y Metabolismo, Facultad de Medicina, Universidad El Bosque, Bogotá, Colombia. [Perdomo,S] International Agency for Research on Cancer, World Health Organization, Lyon, France.
dc.date.accessioned2024-02-12T19:47:58Z
dc.date.available2024-02-12T19:47:58Z
dc.date.issued2020-11-19
dc.description.abstractTriple-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.
dc.description.sponsorshipThis study was funded by grants from UNAM PAPIIT IN219217 and CONACyT Fondo Sectorial 272573.
dc.identifier.doi10.3390/genes11111367
dc.identifier.e-issn2073-4425es_ES
dc.identifier.journalGeneses_ES
dc.identifier.otherhttp://hdl.handle.net/10668/3757
dc.identifier.pubmedID33227964es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/18156
dc.language.isoeng
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)
dc.relation.publisherversionhttps://www.mdpi.com/2073-4425/11/11/1367/htmes
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectTriple-negative breast cancer
dc.subjectWhole exome sequencing
dc.subjectWES
dc.subjectTreatment
dc.subjectSomatic mutation
dc.subjectMutational signatures
dc.subjectNeoplasias de la mama triple negativas
dc.subjectSecuenciación del exoma completo
dc.subjectTerapéutica
dc.subjectNeoplasias de la mama
dc.subjectMéxico
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshDNA Repair-Deficiency Disorders
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshKaplan-Meier Estimate
dc.subject.meshLymphocytes, Tumor-Infiltrating
dc.subject.meshMiddle Aged
dc.subject.meshBreast Neoplasms
dc.subject.meshSequence Analysis, DNA
dc.subject.meshMutation
dc.subject.meshTriple Negative Breast Neoplasms
dc.subject.meshMexico
dc.titleComprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication
relation.isAuthorOfPublication604afbdd-9fa0-469e-acc0-388ec79f9490
relation.isAuthorOfPublication.latestForDiscovery604afbdd-9fa0-469e-acc0-388ec79f9490
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