1176.0 days) in ECM mut patients compared to ECM WT patients. E PFS was significantly shorter (median PFS 938.0 vs. Information on protein structure and domains was obtained from the Uniprot knowledgebase. For all other ECM molecules and more information on mutations see Fig. D Visual representation of domains and structure of proteins encoded by the three ECM genes most recurrently affected by mutations: COL6A3, LAMA1 and ADAMTS20. Non-protein-coding genes were excluded from the analysis (Table S1). C ECM genes contained significantly more SNVs relative to the protein length than other protein-coding genes within the MMRF WES dataset. B STRING network analysis of mutated adhesion genes in our WES study cohort revealed clusters in integrin, collagen, laminin and metalloproteinase genes (ADAMs, ADAMTS). Individual patients are separated by small gaps. Further, cMyc protein expression (orange), del17p status (red), overall high-risk status at diagnosis (a.d.) (light pink) and at biopsy (a.b.) (dark pink) and information on the presence of extramedullary disease (EMD) (salmon) are shown. 1C) which revealed significantly more SNVs per protein length in ECM genes compared to non-ECM genes ( p = 0.000002), suggesting that ECM mutations might be potential cancer driver mutations.Ī Representation of the mutation status of patients with and without mutations in adhesion genes (blue), ECM genes (green) (ECM mut and ECM WT) and the TMB (yellow). Thus, we determined the number of SNVs per protein length in all protein-coding genes sequenced within the Multiple Myeloma Research Foundation (MMRF) CoMMpass study (IA15 cohort 1192 samples from 984 MM patients) and performed a Mann-Whitney- U test (Fig. Since the ECM gene families contain a total of 121 protein-coding genes covering a notable genomic area, we aimed to prove that there are more mutations within ECM genes than would be expected by chance. Subsequent STRING network analysis for the mutated adhesion genes using high confidence settings revealed a clustering of SNVs in gene families associated with the extracellular matrix (ECM): Integrins, collagens, laminins, A disintegrin and metalloprotease (ADAM) as well as the ADAM with thrombospondin motifs (ADAMTS) family (Fig. Mutations in adhesion genes were detected in 58 out of 67 samples from 43 patients of our previously published WES cohort (Fig.
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