{"doi":"10.1200/po.19.00332","title":"WNT-Activated Medulloblastomas With Hybrid Molecular Subtypes","abstract":"Molecular characterization of CNS tumors is becoming increasingly important for both diagnostic clarity and prognostication in the practice of neuropathology. Medulloblastomas, in particular, can be divided into 4 core consensus molecular subgroups (ie, WNT-activated, sonic hedgehog [SHH]-activated, group 3 [G3], and group 4 [G4]) based on genetic alterations, methylation profiles, and transcriptional patterns, which predict prognostic outcomes better than histology alone and are increasingly used for medulloblastoma classification.1,2 WNT-activated medulloblastomas are defined by activating mutations in the WNT/β-catenin signaling pathway (eg, CTNNB1 or germline APC), are often associated with loss of chromosome 6, and have the most favorable prognosis. SHH-activated medulloblastomas are denoted by mutations in the SHH pathway (eg, PTCH1, SMO, SUFU), with intermediate or poor prognosis guided by TP53 status. G3 and G4 medulloblastomas are associated with MYC amplification and MYCN or CDK6 amplification, respectively, frequently harbor isochromosome 17q, and have poor prognoses. Notably, individual tumors with highly characteristic driver events (eg, WNT methylation subclass with CTNNB1 mutation) were thought to be readily assigned to a specific methylation or genomic subclass with little genetic overlap between the subgroups.3\r\n\r\nRecently, however, several patients with medulloblastoma have been reported to harbor combined molecular alterations characteristic of both WNT- and SHH-activated tumors.4,5 We report 2 additional patients with medulloblastoma with hybrid subclass features, one with WNT/SHH dual-activation tumors and another, strikingly, with features of WNT, SHH, and isochromosome 17q—a tertiary feature conventionally thought to be characteristic of G3 and G4 medulloblastomas.","journal":"JCO Precision Oncology","year":2020,"id":83394,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":345872,"name":"Peter Pytel","orcid":"0000-0001-9506-4709","position":1,"is_corresponding":false},{"id":228661,"name":"Varshini Vasudevaraja","orcid":"0000-0001-9678-6375","position":2,"is_corresponding":false},{"id":428967,"name":"Eudocia Q. Lee","orcid":"0000-0003-3355-5179","position":3,"is_corresponding":false},{"id":236056,"name":"Matija Snuderl","orcid":"0000-0003-0752-0917","position":4,"is_corresponding":false},{"id":89706,"name":"J. Bryan Iorgulescu","orcid":"0000-0003-1405-3667","position":5,"is_corresponding":false},{"id":1412,"name":"Keith L. Ligon","orcid":"0000-0002-7733-600X","position":6,"is_corresponding":false},{"id":87168,"name":"Jeffrey Helgager","orcid":null,"position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:54:09.383533Z","pmid":"32923883","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}