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http://purl.uniprot.org/citations/32892208http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32892208http://www.w3.org/2000/01/rdf-schema#comment"Mutations in the tumor suppressor CYLD, known to be causative of cylindromas, were recently described in a subset of high-risk (hr) HPV-positive head and neck squamous cell carcinomas (HNSCC). Pathologic and genetic characterization of these CYLD-mutant carcinomas, however, remains limited. Here, we investigated whether CYLD mutations characterize a histopathologically and genomically distinct subset of hrHPV-positive HNSCC. Comprehensive genomic profiling via hybrid capture-based DNA sequencing was performed on 703 consecutive head and neck carcinomas with hrHPV sequences, identifying 148 unique cases (21%) harboring CYLD mutations. Clinical data, pathology reports, and histopathology were reviewed. CYLD mutations included homozygous deletions (n = 61/148; 41%), truncations (n = 52; 35%), missense (n = 26; 18%) and splice-site (n = 9; 6%) mutations, and in-frame deletion (n = 1; 1%). Among hrHPV-positive HNSCC, the CYLD-mutant cohort showed substantially lower tumor mutational burden than CYLD-wildtype cases (n = 555) (median 2.6 vs. 4.4 mut/Mb, p < 0.00001) and less frequent alterations in PIK3CA (11% vs. 34%, p < 0.0001), KMT2D (1% vs. 16%, p < 0.0001), and FBXW7 (3% vs. 11%, p = 0.0018). Male predominance (94% vs. 87%), median age (58 vs. 60 years), and detection of HPV16 (95% vs. 89%) were similar. On available histopathology, 70% of CYLD-mutant HNSCC (98/141 cases) contained hyalinized material, consistent with basement membrane inclusions, within crowded aggregates of tumor cells. Only 7% of CYLD-wildtype cases demonstrated this distinctive pattern (p < 0.0001). Histopathologic patterns of CYLD-mutant HNSCC lacking basement membrane inclusions included nonkeratinizing (n = 22, 16%), predominantly nonkeratinizing (nonkeratinizing SCC with focal maturation; n = 10, 7%), and keratinizing (n = 11, 8%) patterns. The latter two groups showed significantly higher frequency of PTEN alterations compared with other CYLD-mutant cases (38% [8/21] vs. 7% [8/120], p = 0.0004). Within our cohort of hrHPV-positive HNSCCs, CYLD mutations were frequent (21%) and demonstrated distinctive clinical, histopathologic, and genomic features that may inform future study of prognosis and treatment."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.org/dc/terms/identifier"doi:10.1038/s41379-020-00672-y"xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Williams K.J."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Ross J.S."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Williams E.A."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Tse J.Y."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Alexander B.M."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Glomski K."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Elvin J.A."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Ramkissoon S.H."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Mochel M.C."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Bledsoe J.R."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/author"Montesion M."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/name"Mod Pathol"xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/pages"358-370"xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/title"CYLD mutation characterizes a subset of HPV-positive head and neck squamous cell carcinomas with distinctive genomics and frequent cylindroma-like histologic features."xsd:string
http://purl.uniprot.org/citations/32892208http://purl.uniprot.org/core/volume"34"xsd:string
http://purl.uniprot.org/citations/32892208http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32892208
http://purl.uniprot.org/citations/32892208http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32892208
http://purl.uniprot.org/uniprot/#_A8KAB0-mappedCitation-32892208http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32892208
http://purl.uniprot.org/uniprot/#_B3KNA9-mappedCitation-32892208http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32892208
http://purl.uniprot.org/uniprot/#_B3KND1-mappedCitation-32892208http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32892208
http://purl.uniprot.org/uniprot/#_D6CJC5-mappedCitation-32892208http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32892208
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