%0 Generic
%A Alonso Luna , Oscar 
%A Meléndez Zajgla , Jorge 
%A Zapata Tarres , Marta 
%A Juárez Villegas , Luis Enrique 
%A Mendoza Caamal , Elvia Cristina 
%A Rey Helo, Elianeth 
%A Borges Yanez, Socorro Aida 
%A Mercado Celis, Gabriela Elisa 
%A Barquera Lozano, Rodrigo
%+ Department of Archaeogenetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T Abstract 5219: Frequency of germline mutations in Mexican children with cancer : 
%G eng
%U https://hdl.handle.net/21.11116/0000-000C-EC6B-3
%R 10.1158/1538-7445.AM2022-5219
%D 2022
%Z name of event: American Association for Cancer Research Annual Meeting 2022
%Z date of event: 2022-04-08 - 2022-04-13
%Z place of event: New Orleans
%X Childhood cancer is a leading cause of death by disease in children from 5 -14 ages, for whom there are no prevention strategies. Due to early-age of diagnosis and short-time environmental factors exposition, increasing evidence suggests childhood cancer could have stronger association with germline alterations in predisposition cancer genes. It has been estimated that up to 30% all childhood cancer diagnosis may be caused by germline variants, but their frequency and distribution remain unclear. Elucidating the prevalence and role of germline mutations in the development of childhood cancer is crucial for understanding its bases, causes, cancer-risk reduction plan, surveillance, and treatment. Here, we present a pilot study on cancer children’s patients and their relatives. A total of 40 Mexican-mestizo children with any cancer diagnosis were recruited from several Institutions of Health in Mexico and a sample of saliva or blood was obtained. Whole Exome Sequencing was performed and bioinformatic analysis was carried out following GATK best practices for germline genetic variants. Additionally, we evaluated a risk selection tool for recognition of genetic predisposition in pediatric cancer patients. Pathogenic or likely-pathogenic genetic variants (mutations) were identified from the application of a filtering chain based on ACMG guidelines, and they were subsequently validated by Sanger sequencing. Germline mutations in MSH6, NF1, MUTYH, CDKN2A, CHEK2, DICER1, FANCA and SBDS genes were identified in 5/40 (12.5%) patients with cancer, only 3 of 5 index cases (60%) reported family history of cancer and all patients meet at least one criterion of the risk selection tool. Two patients were carriers of one mutation, while in three patients were identified 2 pathogenic variants. Additionally, we identified four nonsense candidate genetic variants on EWSR1, FANCL, EPCAM and HRAS genes and two pathogenic variants in non-cancer predisposition gene, ABCA4. Our results show for the first time a higher frequency (12.5%) of germline mutations in cancer predisposition genes in Mexican-mestizo children with cancer. The lack of family history in two carriers showed the need to establish standardized suspicion criteria for identification of children with higher risk of cancer who can benefitfrom genetic testing. Further characterization of additional genetic variants identified without clinical classification will be important to evaluate their real contribution, as well as the influence of environmental factors on de novo mutation promotion.
%J Proceedings of the American Association for Cancer Research Annual Meeting 2022
%V 82
%N 12_Supplement
%Z sequence number: 5219
%@ 0008-54721538-7445