AUTHOR=Vázquez-Romo Rafael , Millan-Catalan Oliver , Ruíz-García Erika , Martínez-Gutiérrez Antonio D. , Alvarado-Miranda Alberto , Campos-Parra Alma D. , López-Camarillo César , Jacobo-Herrera Nadia , López-Urrutia Eduardo , Guardado-Estrada Mariano , Cantú de León David , Pérez-Plasencia Carlos 

TITLE=Pathogenic variant profile in DNA damage response genes correlates with metastatic breast cancer progression-free survival in a Mexican-mestizo population

JOURNAL=Frontiers in Oncology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1146008

DOI=10.3389/fonc.2023.1146008

ISSN=2234-943X

ABSTRACT=Metastatic breast cancer most breast-cancer related deaths around the world, especially in countries where breast cancer is detected in late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes, but recent research has shown that mutations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies. We sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing. Overall, we found 22 mutations –9 of them reported for the first time– and a strikingly high proportion of mutations in ARID1A. Mutations in the ARID1A, BRCA1, BRCA2, and FANCA genes were significantly associated with higher progression-free survival in our patient cohort. Thus, our results reflected the unique characteristics of the Mexican-mestizo population as the proportion of mutations we found differ from that of other global populations.  Based on these findings, we suggest routine screening for mutations in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population.