Germline Predisposition to Pediatric Cancer, from Next Generation Sequencing to Medical Care.

Autores de IIS La Fe

• Pablo Gargallo Tatay

  Autor

• Juan Silvestre Oltra Soler

  Autor

• Yania Yañez Peralta

  Autor

• Antonio Juan Ribelles

  Autor

• Vanessa Segura Caballer

  Autor

• Julia Balaguer Guill

  Autor

• Sandra Dolz Giménez

  Autor

• José María Fernández Navarro

  Autor

• Carolina Fuentes Socorro

  Autor

• Bárbara Torres Guerola

  Autor

• Mercedes Andres Celma

  Autor

• Victoria Castel Sánchez

  Autor

• Jaime Font De Mora Sainz

  Autor

• Adela Cañete Nieto

  Autor

Participantes ajenos a IIS La Fe

• Calabria I
• Lázaro M
• Tormo T
• Tasso M

Grupos

• Investigación Clínica y Traslacional en Cáncer

• Investigación Traslacional en Genética

Abstract

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.

Keywords

• genetic counseling, genetic predisposition, genetic syndrome, germline, hereditary cancer, pediatric oncology, working tool