Clinical subtypes and molecular characteristics of serrated polyposis syndrome

Clin Gastroenterol Hepatol. 2013 Jun;11(6):705-11; quiz e46. doi: 10.1016/j.cgh.2012.12.045. Epub 2013 Jan 30.


Background & aims: We investigated clinical and molecular differences between the different phenotypes of serrated polyposis syndrome (SPS) and the frequency of mutations in BRAF or KRAS in polyps from patients with SPS.

Methods: We collected data on clinical and demographic characteristics of 50 patients who fulfilled the criteria for SPS. Polymerase chain reaction and sequence analysis were used to identify BRAF and KRAS mutations in 432 polyps collected from 37 patients; we analyzed CpG island methylator phenotypes in 272 of these polyps.

Results: Fifteen patients (30%) had type 1 SPS and 35 had type 2 SPS. There were no significant differences in age at diagnosis, sex, smoking frequency, body mass index, or colorectal cancer predisposition between groups of patients, or in the pathologic or molecular characteristics of their polyps. A familial history of colorectal cancer or colonic polyps was reported more frequently by patients with type 2 SPS. BRAF mutations were found in 63% of polyps and KRAS mutations were found in 9.9%; 43.4% of polyps had the CpG island methylator phenotype-high phenotype. A per-patient analysis revealed that all patients had a BRAF or KRAS mutation in more than 25% of their polyps; 84.8% of patients had a mutation in BRAF or KRAS in more than 50% of their polyps.

Conclusions: Except for a greater likelihood of familial history of colorectal cancer or colonic polyps in patients with type 2 SPS, we found no significant demographic, pathologic, or molecular differences between types 1 and 2 SPS. All patients had a BRAF or KRAS mutation in at least 25% of their polyps.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / pathology*
  • Adult
  • Aged
  • CpG Islands
  • DNA Methylation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Sequence Analysis, DNA
  • ras Proteins / genetics*


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins

Supplementary concepts

  • Polyposis Syndrome, Hereditary Mixed, 1
  • Polyposis Syndrome, Hereditary Mixed, 2