Germline Predisposition to Pediatric Cancer, from Next Generation Sequencing to Medical Care
Por:
Gargallo, P, Oltra, S, Yanez, Y, Juan-Ribelles, A, Calabria, I, Segura, V, Lazaro, M, Balaguer, J, Tormo, T, Dolz, S, Fernandez, J, Fuentes, C, Torres, B, Andres, M, Tasso, M, Castel, V, de Mora, J and Canete, A
Publicada:
1 nov 2021
Ahead of Print:
24 oct 2021
Resumen:
Simple Summary: The idea that motivated the design of the project is to offer a genetic germline analysis to all pediatric patients diagnosed in our pediatric oncology unit. The main objective is to determine the incidence of predisposing genetic variants when studying a cohort of pediatric cancer patients using an NGS gene panel. The custom panel employed is designed to detect variants in a large number of genes involved in pediatric cancer in order to be able to identify new genotype-phenotype relationships. The data obtained are valuable for estimating the incidence of predisposing genetic alterations, due to the large number of pediatric patients included in the study. Furthermore, the novel results collected in the main document, which suggest the involvement of new genes in the predisposition to different oncological diseases, are worthwhile.Knowledge about genetic predisposition to pediatric cancer is constantly expanding. The categorization and clinical management of the best-known syndromes has been refined over the years. Meanwhile, new genes for pediatric cancer susceptibility are discovered every year. Our current work shares the results of genetically studying the germline of 170 pediatric patients diagnosed with cancer. Patients were prospectively recruited and studied using a custom panel, OncoNano V2. The well-categorized predisposing syndromes incidence was 9.4%. Likely pathogenic variants for predisposition to the patient's tumor were identified in an additional 5.9% of cases. Additionally, a high number of pathogenic variants associated with recessive diseases was detected, which required family genetic counseling as well. The clinical utility of the Jongmans MC tool was evaluated, showing a high sensitivity for detecting the best-known predisposing syndromes. Our study confirms that the Jongmans MC tool is appropriate for a rapid assessment of patients; however, the updated version of Ripperger T criteria would be more accurate. Meaningfully, based on our findings, up to 9.4% of patients would present genetic alterations predisposing to cancer. Notably, up to 20% of all patients carry germline pathogenic or likely pathogenic variants in genes related to cancer and, thereby, they also require expert genetic counseling. The most important consideration is that the detection rate of genetic causality outside Jongmans MC et al. criteria was very low.
Filiaciones:
Gargallo, P:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Imegen Hlth Code Grp, Dept Oncol, Valencia 46980, Spain
Oltra, S:
Hosp Univ & Politecn La Fe Valencia, Genet Unit, Valencia 46026, Spain
Univ Valencia, Genet Dept, Valencia 46010, Spain
Yanez, Y:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Juan-Ribelles, A:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Calabria, I:
Imegen Hlth Code Grp, Dept Oncol, Valencia 46980, Spain
Segura, V:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Lazaro, M:
Imegen Hlth Code Grp, Dept Oncol, Valencia 46980, Spain
Balaguer, J:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Tormo, T:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Dolz, S:
Inst Invest Sanitaria La Fe, Lab Cellular & Mol Biol, Clin & Translat Res Canc, Valencia 46026, Spain
Fernandez, J:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Fuentes, C:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Torres, B:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
:
Hosp Gen Alicante, Pediat Oncol Dept, Alicante 03010, Spain
Castel, V:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
de Mora, J:
Inst Invest Sanitaria La Fe, Lab Cellular & Mol Biol, Clin & Translat Res Canc, Valencia 46026, Spain
Canete, A:
Hosp Univ & Politecn La Fe Valencia, Pediat Oncol Dept, Valencia 46026, Spain
Univ Valencia, Dept Pediat Obstet & Gynecol, Valencia 46010, Spain
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