Rothmund-thomson syndrome and cutan T-cell lymphoma in childhood

We report a 3-year-old girl suffering from RothmundThomson Syndrome (RTS). The patient at birth had multiplex anomalies: poikilodermatous rash, sceletal abnormalities: palatoschisis, micrognathi, aplasia radii, hypoplastic right and left thenar and thumbs, pesequinus on both site, ectopy renis. The patient in the later ages was detected dental malformation, facial dysmorfism. At the age 3, she had lasion in her muscle. After biopsy, histological examination showed cutan T-cell lymphoma. The patient is the first case who had cutan T-cell lymphoma associated with RTS in this young age.

Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors

Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support methods.Digital drug assignment(DDA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted agents.DDA has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical trial.The aim of this study was to evaluate the utility of DDA in pediatric oncology.Methods Between 2017 and 2020,103 high-risk pediatric cancer patients(<21 years)were involved in our precision oncology program,and samples from 100 patients were eligible for further analysis.Tissue or blood samples were analyzed by whole-exome(WES)or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision support.Finally,a molecular tumor board(MTB)evaluated the results to provide therapy recommendations.Results Of the 100 cases with comprehensive molecular diagnostic data,88 yielded WES and 12 panel sequencing results.DDA identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug resistance.Actionability reached 88%(29/33)by 2020 due to the continuous updates of the evidence database.MTB approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed therapies.Filtering of WES results for targeted panels missed important mutations affecting therapy selection.Conclusions DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine care of high-risk pediatric cancers.Knowledgebase updates enable automatic interpretation of a continuously expanding gene set,a“virtual”panel,filtered out from genome-wide analysis to always maximize the performance of precision treatment planning.