Analysis of Mutation and Loss of Heterozygosity by Whole-Exome Sequencing Yields Insights into Pseudomyxoma Peritonei

J Mol Diagn. 2018 Sep;20(5):635-642. doi: 10.1016/j.jmoldx.2018.05.002. Epub 2018 Jun 22.


Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by gross mucinous ascites originating from a disseminated intraperitoneal neoplasm. Although typically confined to the abdomen, mortality is high if untreated. Biomarkers, including genetic mutation profiles, may aid treatment selection and decision making. We applied whole-exome sequencing to five patients diagnosed with low-grade appendiceal mucinous neoplasms, using paired tumor and germline samples identify biomarkers. Multiple bioinformatic approaches were applied to these data to assess both somatic mutation profiles and loss of heterozygosity events. Mutation profiles of the tumors were consistent with deamination of methylcytosine being the prevailing mechanism. Pathogenic mutations were identified in both KRAS and GNAS in all samples, and further mutations in genes implicated in PMP, namely FGFR2, APC, SMAD2, and FAT4. No TP53 somatic mutations were identified, matching expectations for low-grade tumors. Four of five samples exhibited clonal loss of heterozygosity; these regions were further examined and found to contain genes harboring pathogenic somatic mutations in some samples. RNF43 was hereby implicated in the pathogenesis of PMP of appendiceal origin, having previously been found to increase sensitivity to Wnt signaling and to have involvement in similar mucinous tumors. In conclusion, we have investigated the mutation profile of PMP of appendiceal origin and provided the first report of RNF43 involvement in its progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Chromosomes, Human, Pair 17 / genetics
  • Female
  • Gene Frequency / genetics
  • Humans
  • Loss of Heterozygosity / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Peritoneal Neoplasms / diagnosis
  • Peritoneal Neoplasms / genetics*
  • Peritoneal Neoplasms / pathology
  • Pseudomyxoma Peritonei / diagnosis
  • Pseudomyxoma Peritonei / genetics*
  • Pseudomyxoma Peritonei / pathology
  • Whole Exome Sequencing / methods*


  • Biomarkers, Tumor