FaCD Online Syndrome Fact Sheet

Last updated: 11 Aug 2011

Name: Familial Serrated Neoplasia

Synonym: Jass syndrome, Serrated Pathway Syndrome, incl. Serrated Adenomatous Polyposis, Serrated Polyposis

Mode of Inheritance: AD? Multifact?

Tumor features

colorectal adenomas
colorectal cancer
colorectal hyperplastic polyps
serrated adenomas, colorectal


Torlakovic and Snover[1] have drawn attention to the fact that patients originally classified as having hyperplastic polyposis of the colon may actually have polyps which are more similar to serrated adenomas[2] than to true hyperplastic polyps. Yao et al.[3] reported a 70-year-old woman who was diagnosed with 6 carcinomas of the right colon, surrounded by serrated as well as hyperplastic polyps. They described the carcinomas as ‘colonic carcinoma with gastric differentiation’, which they proposed as a new subtype.

The serrated pathway has been identified as one of the pathways in sporadic colorectal cancer development and is charcterized by early involvement of oncogenic BRAF mutations, excess CpG island methylation and low- or high-level DNA microsatellite instability[4,5]. Jass and colleagues identified familial clustering of colorectal cancer following this serrated pathway and coined the name serrated pathway syndrome[6,7]. These familial show colorectal cancer, sparse serrated polyps and adenomas with occasionally hyperplastic polyposis. The authors distinguish this disorder from hyperplastic polyposis which in their opinion also follows the serrated pathway but typically has more polyps, weaker familial clustering with "recessive" rather than "dominant" patterns. Serrated polyps appear to be rare in Lynch syndrome and familial colorectal cancer families[8].

A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped[9]. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage(HLOD 2.09; NonParametricLinkage 2.36 (P = 0.004)).


[1] Torlakovic E, Snover DC. Serrated adenomatous polyposis in humans. GASTROENTEROLOGY 1996; 110:748-755.
[2] Matsumoto T, Mizuno M, Shimizu M, Manabe T, Iida M, Fujishima M. Serrated adenoma of the colorectum: Colonoscopic and histologic features. Gastrointest Endosc 1999; 49(6):736-742.
[3] Yao T, Nishiyama Ki, Oya M, Kouzuki T, Kajiwara M, Tsuneyoshi M. Multiple 'serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation. J Pathol 2000; 190(4):444-449.
[4] Mäkinen MJ. Colorectal serrated adenocarcinoma. Histopathology 2007; 50(1):131-50.
[5] Kambara T, Simms LA, Whitehall VL, Spring KJ, Wynter CV, Walsh MD, Barker MA, Arnold S, McGivern A, Matsubara N, Tanaka N, Higuchi T, Young J, Jass JR, Leggett BA. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 2004; 53(8):1137-44.
[6] Young J, Jass JR. The case for a genetic predisposition to serrated neoplasia in the colorectum: hypothesis and review of the literature. Cancer epidemiology, biomarkers & prevention 2006; 15(10):1778-84.
[7] Young J, Barker MA, Simms LA, Walsh MD, Biden KG, Buchanan D, Buttenshaw R, Whitehall VL, Arnold S, Jackson L, Kambara T, Spring KJ, Jenkins MA, Walker GJ, Hopper JL, Leggett BA, Jass JR. Evidence for BRAF mutation and variable levels of microsatellite instability in a syndrome of familial colorectal cancer. Clinical gastroenterology and hepatology 2005; 3(3):254-63.
[8] Andersen SH, Lykke E, Folker MB, Bernstein I, Holck S. Sessile serrated polyps of the colorectum are rare in patients with Lynch syndrome and in familial colorectal cancer families. Familial cancer 2008; 7(2):157-62.
[9] Roberts A, Nancarrow D, Clendenning M, Buchanan DD, Jenkins MA, Duggan D, Taverna D, McKeone D, Walters R, Walsh MD, Young BW, Jass JR, Rosty C, Gattas M, Pelzer E, Hopper JL, Goldblatt J, George J, Suthers GK, Phillips K, Parry S, Woodall S, Arnold J, Tucker K, Muir A, Drini M, Macrae F, Newcomb P, Potter JD, Pavluk E, Lindblom A, Young JP. Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome). Fam Cancer. 2011 Jun;10(2):245-54.