Whole-genome analysis of de novo somatic point mutations reveals novel mutational biomarkers in pancreatic cancer

Ghareyazi, A ; Sharif University of Technology | 2021

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  1. Type of Document: Article
  2. DOI: 10.3390/cancers13174376
  3. Publisher: MDPI , 2021
  4. Abstract:
  5. It is now known that at least 10% of samples with pancreatic cancers (PC) contain a causative mutation in the known susceptibility genes, suggesting the importance of identifying cancer-associated genes that carry the causative mutations in high-risk individuals for early detection of PC. In this study, we develop a statistical pipeline using a new concept, called gene-motif, that utilizes both mutated genes and mutational processes to identify 4211 3-nucleotide PC-associated gene-motifs within 203 significantly mutated genes in PC. Using these gene-motifs as distinguishable features for pancreatic cancer subtyping results in identifying five PC subtypes with distinguishable phenotypes and genotypes. Our comprehensive biological characterization reveals that these PC subtypes are associated with different molecular mechanisms including unique cancer related signaling pathways, in which for most of the subtypes targeted treatment options are currently available. Some of the pathways we identified in all five PC subtypes, including cell cycle and the Axon guidance pathway are frequently seen and mutated in cancer. We also identified Protein kinase C, EGFR (epidermal growth factor receptor) signaling pathway and P53 signaling pathways as potential targets for treatment of the PC subtypes. Altogether, our results uncover the importance of considering both the mutation type and mutated genes in the identification of cancer subtypes and biomarkers. © 2021 by the authors. Licensee MDPI, Basel, Switzerland
  6. Keywords:
  7. Biological marker ; Epidermal growth factor receptor ; Protein kinase C ; Protein p53 ; Axon guidance ; Carcinogenesis ; Cell cycle ; EGFR signaling ; Female ; Human ; Human cell ; Major clinical study ; Male ; Molecularly targeted therapy ; P53 signaling ; Pancreas cancer ; Point mutation ; Protein analysis ; Whole genome sequencing
  8. Source: Cancers ; Volume 13, Issue 17 , 2021 ; 20726694 (ISSN)
  9. URL: https://www.mdpi.com/2072-6694/13/17/4376