DNA Methylation Analysis of the PDX1 Gene Can Be Used for PNET Subtyping and Has a Possible Prognostic Value
Introduction: Estimating prognosis of pancreatic neuroendocrine tumor (PNET) patients remains challenging. Mutation status of DAXX/ATRX/MEN1, histone modification patterns and immunohistochemistry for relevant transcription factors, including PDX1, were recently used to perform subtyping and distinguished two main types, A and B. These subtypes are linked to cell-of-origin and associated with clinical outcome.
Aim(s): In this study, we assessed whether DNA methylation of PDX1 can be used to identify the A and B subtypes and tested their prognostic value.
Materials and methods: DNA methylation analysis using Infinium MethylationEPIC and 450K arrays (Illumina) was performed on DNA from tissue of 41 PNETs. Additional methylation data of 42 PNETs and healthy alpha and beta cells were collected through public databases. Methylation values of CpGs in the PDX1 region were used to perform clustering to identify subtypes for survival analysis. Available clinicopathological and sequencing data were included in the analyses.
Conference: 17th Annual ENETSConcerence (2020)
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