The Burden of Post-Translational Modification (PTM)-Disrupting Mutations in the Tumor Matrisome.

Background: To evaluate the occurrence of mutations affecting post-translational modification (PTM) sites in matrisome genes across different tumor types, in light of their genomic and functional contexts and in comparison with the rest of the genome.
Methods: This study spans 9075 tumor samples and 32 tumor types from The Cancer Genome Atlas (TCGA) Pan-Cancer cohort and identifies 151,088 non-silent mutations in the coding regions of the matrisome, of which 1811 affecting known sites of hydroxylation, phosphorylation, N- and O-glycosylation, acetylation, ubiquitylation, sumoylation and methylation PTM.
Results: PTM-disruptive mutations (PTM ^mut ) in the matrisome are less frequent than in the rest of the genome, seem independent of cell-of-origin patterns but show dependence on the nature of the matrisome protein affected and the background PTM types it generally harbors. Also, matrisome PTM ^mut are often found among structural and functional protein regions and in proteins involved in homo- and heterotypic interactions, suggesting potential disruption of matrisome functions.
Conclusions: Though quantitatively minoritarian in the spectrum of matrisome mutations, PTM ^mut show distinctive features and damaging potential which might concur to deregulated structural, functional, and signaling networks in the tumor microenvironment.