Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology.
Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review su…
Clinical and genetic risk factors define two risk groups of extracranial malignant rhabdoid tumours (eMRT/RTK)
Abstract Introduction Extracranial rhabdoid tumours are rare, highly aggressive malignancies primarily affecting young children. The EU-RHAB registry was initiated in 2009 to prospectively collect data of rhabdoid tumour patients treated according to the EU-RHAB therapeutic framework. Methods We evaluated 100 patients recruited within EU-RHAB (2009–2018). Tumours and matching blood samples were examined for SMARCB1 mutations by sequencing and cytogenetics. Results A total of 70 patients presented with extracranial, extrarenal tumours (eMRT) and 30 with renal rhabdoid tumours (RTK). Nine patients demonstrated synchronous tumours. Distant metastases at diagnosis (M+) were present in 35% (35/1…
Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers.
Abstract Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression–based classification and established prognostic markers. Experimental Design: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4 × 44 K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n = 634) by Kaplan–Meier estimates and Cox regression analyses. Results: The best-performing classifier predicted patient outcome with an accuracy of 0.95 (sensitivity, 0.93; specificity, 0.97) in the validation coh…
Risk estimation in localized unresectable single copy MYCN neuroblastoma by the status of chromosomes 1p and 11q
In localized neuroblastoma, the identification of patients requiring intensive treatment is still difficult. We retrospectively analyzed data of 280 single copy MYCN stage 2 and 3 neuroblastoma patients with gross residual tumor after initial surgery. The 3-year-event free survival of the total group was 83+/-2%, and 3-year-overall survival was 92+/-2%. Patients < or=1.5 years had a better outcome than older children. Deletions/imbalances of chromosome 1p were found in 9/90 patients and were associated with a higher event rate but not with a higher death rate. Aberrations of chromosome 11q in 14/91 patients were correlated with a higher event and death rate. Multivariate analysis identified…