Dr. Cheung
Summer interns at the presentation
Thank you Dr. Nai-Kong Cheung, Enid A. Haupt Chair in Pediatric Oncology, #MSKKids, @mskcancercenter.bsky.social, for giving our summer interns an inspiring lecture on #immunotherapy and the journey to develop better treatments in pediatric care.
Join us for a complimentary, in-person symposium to explore the latest research and innovative treatments tailored to the distinct needs of the adolescent and young adult (AYA) cancer population. The symposium will focus on 3 core themes: 🔹Translating biological discoveries into clinical practice 🔹 Innovations in supportive services to enhance quality of life 🔹 Emerging interventional studies in AYA oncology
Join us for a complimentary, in-person symposium @mskcancercenter.bsky.social to explore the latest research and innovative treatments tailored to the distinct needs of the adolescent and young adult (#AYA) cancer population: bit.ly/AYASymposium2025
#MSKAYACME #AYA #MSKkids
Great end to the Steel Symposium. Congratulations to the organizers for putting together a meeting that covered much of the pediatric oncology landscape and kept people engaged. Abstracts for next year open in the fall. #MSKDevOnc #MSKkids
Pfister - So is there a way to detect this earlier. In summary, large CNVs may initiated many pediatric tumors, before birth. Oncogenic drivers are needed for tumor progression but not initiation. The MYC clones are further selected under treatment pressure. Clonal organpoiesis! #MSKDevOnc #MSKkids
Pfister - High grade gliomas and other solid tumors. See date of origin in early common ancestor before birth. The pediatric tumors all look similar. Need some type of early trigger that convert. This looks very different from carcinomas and GBM that are all post birth. #MSKDevOnc #MSKkids
Pfister - can see tumors that at the expression level have both MYCN and MYC expression in different cells. Also looked at primary and relapse sample. At relapse the MYC clone had outgrown the MYCN and oncogene negative clones. See that in other MB tumors at relapse. #MSKDevOnc #MSKkids
Pfister - Medulloblastoma age of onset and MRCA match the average age of diagnosis of different MB subtypes. Many may begin during end of 1st trimester. Long phase of pre-malignant clone during childhood. MYC/MYCN/PRDM6 take longer consisten with older onset. #MSKDevOnc #MSKkids
Pfister - Medulloblastoma 3/4 recurrent CNVs not SNVs. Early paper that tetrapolidization was an early event. 17 oncogene positive MYC/MYCN/PRDM6 subset. CNV from snATAC data - InferCNV. See sub clonal MYCN amplified preceded by CNVs. Similar for MYC amplification. #MSKDevOnc #MSKkids
Richard Phillips - UPenn - epigenetic dysregulation of midline brain tumors. Different epigenetic regulator changes with age. Where K3.1 K27M is much younger than K3.3G34R/V tumors. IDH mutant is even older adults. Vulnerable periods of plasticity may differ. #MSKDevOnc #MSKkids
Piyush Joshi - German Cancer Research Center. Plasticity of Medulloblastoma Group 3/4. See overlapping molecular programs across subtypes. Single nucleus multi-omic experiments. Transcription factor network. #MSKDevOnc #MSKkids
Teachey - T-ALL stratification - not nearly as well developed as for B-ALL. COG, St. Jude study trying to analyze patients at diagnosis - WES, transcriptome, WGS germline 900 cases. Immunophenotying. Focus on talk bulk genomics. Little WGS data and excluded relapse patients. #MSKDevOnc #MSKkids
David Teachey - CHOP on pediatric ALL treatment. Most of initial treatments developed in 1950’s. Hit a threshold with standard CTX in COG trials that ended in the 90’s, Focus on T-ALL - one good shot for initial treatment. Relapse not very successful. Need to improve frontline #MSKDevOnc #MSKkids
Soulier - New condition due to ERCC6L2 syndrome with microcephaly and MDS/AML consanguineous families. Skin cancers followed by MDS/AML. Also see with XPC delTG. Stressed hematopoiesis p53 activation. See similar pathway of mutational events. Mentions new paper on ATR rescue #MSKDevOnc #MSKkids
Soulier - Cells can’t resolve DNA damage and go into senescence by activation of p53/p21. Can see signs of this very early in life. Accumulate damage along life and by 6-7 years see BMF and clonal evolution. Known for years that cells can revert and repopulate. #MSKDevOnc #MSKkids
Jean Soulier - France Genomic Instability in MDS/Fanconi Anemia begins Day 2 of the Steel Symposium. Now up to 24 genes. See both MDS and AML with subsequent in adults get solid tumors H&N SCC. Aldehydes one cause of inter strand crosslinks. #MSKDevOnc #MSKkids
Northcott - still some cases when doing molecular anlaysis there are some briding cases of MB and pinealblastoma. Some genes are unregulated in MB, RB and Pinealblastoma. Oncogenic photoreceptor group of genes. Look along the trajectories and see active in all 3 lineages. #MSKDevOnc #MSKkids
Paul Northcott - St. Jude - reviewing the history of the Medulloblastoma molecular anlaysis. 4 groups go back to many papers in 2006 to 2011. 2016 WHO classification separate out these diseases. Origins of MB for Group 3 & 4. #MSKDevOnc #MSKkids
Pallavi Mohapatra - Huangfu and Ziv labs. Pancreatic Neuroendocrine tumors. Highly heterogeneous depending on the type of Islet cells and the hormone expressed (10-40% of tumors). Remainder are non-expressing and diagnosed very extensive. Lack of targeted therapeutic options. #MSKDevOnc #MSKkids
Taryn Treger - UK - Wilms Tumor genetic predisposition. Compared WGS to 71 children with Wilms tumor with some known anomalies and similar number that were “negative”. Look at what is missed by standard analysis. #MSKDevOnc #MSKkids
Vasileva - Mesenchymal cell marker increase (tbxta - Brachyury) in NCC EWSR1:FLI1+ cells. These cells also undergo abnormal migration during early development and impacts fin development. #MSKDevOnc #MSKkids
Vasileva - Xenopus model of EWSR-FLI1 expression and look at cellular impact. Neural crest cells (NCCs) tolerate it. Can see NCCs double labeled for EWSR-FLI1 expression. See invasive tumors develop with some evidence for mets with mesenchymal features. BioRxiv 2024 #MSKDevOnc #MSKkids
Elena Vasileva - Amatruda Lab at Children’s Hospital LA. Working on molecular genetics of Ewing sarcoma. No previously available mouse genetic model. EWS-Fli is very toxic in mouse cells. Using Zebrafish as a mosaic model instead. Inducible model (Elife, 2022). #MSKDevOnc #MSKkids
Steinberg - Not surprisingly is that many non-canonical ORFs found by proteomics in these genes found in the alternative splice products from tlong-read RNAs from tumors. Looking at DSCRT samples. Also see productives related to fusion proteins #MSKDevOnc #MSKkids
Steinberg - in pilot have short read and long read (ONT) from a subset of tumors to see what is gained. Many short-read assemblies are lacking in long-read assemblies. In long-read see very diverse splicing events. Compared to proteomics timsTOF Ultra DIA MS proteomics. #MSKDevOnc #MSKkids
Asher Steinberg - Kentsis lab Long read sequencing of sarcomas. Osteosarcoma high number of rearrangements but few point mutations. Doing long-read RNA sequencing to capture different isoforms by looking at splice junctions to get better patterns than short reads. #MSKDevOnc #MSKkids
Lauren Banks - MSKCC - breaking HLA restriction and using TCR to attack intracellular antigen. Desmoplastic small cell round cell tumor. EWSR1-WT1 defines this tumor type. Conserved exon sequence of fusion RNA. So have a specific and unique junction peptide fragment. #MSKDevOnc #MSKkids
Fujino - UT snRNP200 Car-T cells in mouse models show decrease in AML progression and cells are activated and proliferative. Looking at their impact on B cell models (90% of patients express this marker). Their scFv is derived from antibodies found in disease-free AML patients. #MSKDevOnc #MSKkids
Takeshi Fujino - MSKCC Pharmacology. Taking on Development of CAR-T cells targeting U5 snRNP200 for AML and b-lymphoid malignancies. Anti-U5 snRNP200 antibodies are being used. U5 snRNP200 is an RNA helicase part of the spliceosome. #MSKDevOnc #MSKkids
Kong - ICAM1 is a reliable marker for latency conversion in response to decitibine and measuring it in response to DNMT1 inhibitor induced latency conversion. Many transcription factors play a role and assessing which are potential targets to increase transition. #MSKDevOnc #MSKkids
Isabella Kong - Roth Lab - Weill Cornell Medicine. EBV-associated lymphoma. EBV latency states in malignancies. Latency 2 and 3 more likely to be killed by EBV specific killing. Latency 1 tumors don’t express antigens. Get partial conversion from latency 1 tumors by decitabine. #MSKDevOnc #MSKkids
