Table 2.

Features of colorectal cancer predispositions involving BRAF mutation and hypermethylation

FeaturesHPPSPSSporadic CIMP CRC
MSI status of CRCPredominantly MSS with occasional MSI-L and MSI-H (44, 45, 91)Predominantly MSS with occasional MSI-L and MSI-H CRC (63)At least 50% are MSI-H and the remainder are MSI-L or MSS (93)
Precursor lesionsMultiple serrated polyps and a lesser number of adenomas (51)Sparse serrated polyps and adenomas present. Occasional individual has HPPSSA (12). May present with synchronous serrated polyps and adenomas
Sex ratio and age of onsetEqual sex ratios, 54 yFemale preponderance, 58 yFemale preponderance, 74 y
Family historyOccasional first-degree relative with colorectal cancer (51), rare sibships, suggestive of codominant or recessive inheritanceMulticase colorectal cancer family, Amsterdam-like configurationNo family history
BRAF mutationUp to 66% of lesions (59)Up to 70% of lesionsIn virtually all MSI-H CRC and up to 75% of the remainder
MethylationCIMP is common (58, 59)Methylation of MINT31 80%. Methylation of MLH1 in all MSI-H casesWidespread CIMP
  • Abbreviation: CRC, colorectal cancer.