Genetic predisposition to childhood cancer: A retrospective cohort analysis in a multidisciplinary genetic cancer counseling Unit.

Abstract

e13643 Background: The incidence of childhood cancer in Spain is 18, 2 cases per 100.000 inhabitants per year. The presence of predisposing genetic factors has been revealed in approximately 10% of patients, in them the detection of genetic mutations associated is essential in order to establish the correct clinical management of patients and their relatives. However, genetic counseling in this population is currently underestimated since, not all patients with pediatric malignancies have a family history of cancer or other clinical signs to suspect and inheritance syndrome. Methods: The Unit for Predisposition to Child and Adolescent Cancer of the University Hospital La Paz in Madrid, Spain, is composed by the Units of Clinical Oncology, Pediatric Hemathology-Oncology, and Genetics. Inclusion criteria are based on the characteristics of the individual's neoplasia, family characteristics and other phenotypic characteristics.The molecular study is carried out through Next Generation Sequencing, Direct Sequencing and / or MLPA. In the present study, a retrospective and descriptive analysis of the cases studied from September 2018 to December 2019 was carried out. Results: The Pediatric Cancer Predisposition Functional Unit of the La Paz University Hospital attended during the years 2018 and 2019 a 58 patients with suspected predisposition syndromes to childhood cancer belonging to 41 families. The following inheritance syndromes have been identified: hereditary retinoblastoma in 14 families with mutation in the RB1 gene, Li Fraumeni syndrome in 1 family with mutation in the TP53 gene, multiple endocrine neoplasia type 2A by RET gene mutation in 1 family, 1 hereditary melanoma syndrome with a CDKN2A mutation, and inheritance family leukemia in 1 family with a PAX5 gene mutation. Other cases studied have been negative-non informative, with the following neoplasms of the index cases: unilateral retinoblastoma, hepatoblastoma, hamartomatous colon polyposis, lymphoma, leukemia and soft tissue sarcoma. In addition to the molecular diagnosis of the index case, both cases and family members received genetic counseling and adequate clinical management, adapted to each syndrome. Conclusions: The multidisciplinary and specialized approach improves the diagnosis and monitoring of patients with suspected syndromes of predisposition to childhood cancer and allows the establishment of prevention strategies and early diagnosis individualized to each family.