American Association for Cancer Research
Browse

Supplementary table from Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression

Download (164.9 kB)
dataset
posted on 2023-04-03, 16:21 authored by Lauren Edwards, Rohit Gupta, Fabian Volker Filipp

SI_01_Patient_Cohort Patient barcodes and datasets of SKCM TCGA project SI_02_WES_DPYD Patient barcodes pf WES data and mutational status of DPYD SI_03_Clinical_Data Clinical data of pharmaceutical drugs and therapy types of patients in SKCM TCGA project SI_04_PYR_LOG2RNASEQ Log2 RNASEQ gene expression data of genes in pyrimidine pathway KEGG ID:00240 SI_05_PYR_MUTSIG Functional somatic mutations of genes in pyrimidine pathway KEGG ID:00240 in TCGA SKCM project SI_06_PAN_DPYD_MUTSIG Functional somatic mutations in DPYD in TCGA PAN-cancer project SI_07_Somatic_Mutations_DPYD Structural analysis of somatic mutations in DPYD in TCGA PAN-cancer project SI_08_DPYD_Melanoma_Progression Differences of Log2 RNASEQ gene expression between patients with WT and mutational status of DPYD in TCGA SKCM SI_09_Glossary and_GeneSymbols Glossary of Gene Symbols and NCBI Gene IDs of pyrimidine pathway and oncogenes identified SI_01-03 Pivot table organizing TCGA barcodes, utilized NGS and clinical data of SKCM cohort SI_04-05 Pivot table showing significant deregulation of gene expression and occurance of somatic mutations in pyrimidine pathway Average log2 RSEM RNASeq data is sorted by significant changes between metastatic (TM) and primary (TP) tumors NCBI Gene ID is used to catalogue genes; discrepancies between RNASeq transcript Gene Symbols and IDs are highlighted SI_06-08 Pivot table showing significance of somatic mutations in DPYD across Pan Cancer TCGA project Pivot table listing somatic mutations of DPYD, solvent accessible surface area, and functional impact by PPH2 Pivot table showing enrichment of pathway deregulation.

Funding

NIH

NCI

History

ARTICLE ABSTRACT

New strategies are needed to diagnose and target human melanoma. To this end, genomic analyses was performed to assess somatic mutations and gene expression signatures using a large cohort of human skin cutaneous melanoma (SKCM) patients from The Cancer Genome Atlas (TCGA) project to identify critical differences between primary and metastatic tumors. Interestingly, pyrimidine metabolism is one of the major pathways to be significantly enriched and deregulated at the transcriptional level in melanoma progression. In addition, dihydropyrimidine dehydrogenase (DPYD) and other important pyrimidine-related genes: DPYS, AK9, CAD, CANT1, ENTPD1, NME6, NT5C1A, POLE, POLQ, POLR3B, PRIM2, REV3L, and UPP2 are significantly enriched in somatic mutations relative to the background mutation rate. Structural analysis of the DPYD protein dimer reveals a potential hotspot of recurring somatic mutations in the ligand-binding sites as well as the interfaces of protein domains that mediated electron transfer. Somatic mutations of DPYD are associated with upregulation of pyrimidine degradation, nucleotide synthesis, and nucleic acid processing while salvage and nucleotide conversion is downregulated in TCGA SKCM.Implications: At a systems biology level, somatic mutations of DPYD cause a switch in pyrimidine metabolism and promote gene expression of pyrimidine enzymes toward malignant progression. Mol Cancer Res; 14(2); 196–206. ©2015 AACR.

Usage metrics

    Molecular Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC