• hereditary non-polyposis colorectal cancer
• adenomas
• dysplasia
• mismatch repair
• proximal colon
• adenoma-carcinoma sequence

In this issue of Gut, Rijcken and colleagues¹ compare adenomas found in hereditary non-polyposis colorectal cancer (HNPCC) patients with those found in patients without a family history of colorectal cancer [see 382]. HNPCC is an autosomal dominant syndrome associated with an increased risk of cancer at a number of anatomical sites but most noticeably of the bowel and endometrium. Some of the HNPCC adenomas examined in this study were derived from patients in families with known germline mutations in a DNA mismatch repair (MMR) gene (this topic has been reviewed recently in Gut by Wheeler and colleagues² ). Colorectal carcinoma in patients with germline MMR mutations exhibit failure of DNA MMR as a result of loss of expression of both copies of the MMR gene. Failure of DNA repair implies that particular DNA sequences, if mutated somatically, are less likely to be corrected.²

There are three notable features of carcinomas arising as a result of HNPCC: (i) an excess of proximal lesions, (ii) an excess of mucinous and undifferentiated lesions, and (iii) evidence of rapid progression rates for …