DNA methylation-based classification of sinonasal undifferentiated carcinoma.

ABSTRACT: Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy harboring IDH2 R172 mutations in >80% cases. We explored the potential of genome-wide DNA methylation profiling to elucidate tumor biology and improve the diagnosis of sinonasal undifferentiated carcinoma and its histologic mimics. Forty-two cases, including sinonasal undifferentiated, large cell neuroendocrine, small cell neuroendocrine, and SMARCB1-deficient carcinomas and olfactory neuroblastoma, were profiled by Illumina Infinium Methylation EPIC array interrogating >850,000 CpG sites. The data were analyzed using a custom bioinformatics pipeline. IDH2 mutation status was determined by the targeted exome sequencing (MSK-IMPACTTM) in most cases. H3K27 methylation level was assessed by the immunohistochemistry-based H-score. DNA methylation-based semi-supervised hierarchical clustering analysis segregated IDH2 mutants, mostly sinonasal undifferentiated (n?=?10) and large cell neuroendocrine carcinomas (n?=?4), from other sinonasal tumors, and formed a single cluster irrespective of the histologic type. t-distributed stochastic neighbor embedding dimensionality reduction analysis showed no overlap between IDH2 mutants, SMARCB1-deficient carcinoma and olfactory neuroblastoma. IDH2 mutants demonstrated a global methylation phenotype and an increase in repressive trimethylation of H3K27 in comparison to IDH2 wild-type tumors (p?

SUBMITTER: Dogan S 

PROVIDER: S-EPMC7391258 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature