MUTYH associated polyposis (MAP, MIM 604933)
Familial adenomatous polyposis is a well-described autosomal dominant inherited syndrome with near-complete penetrance associated with APC. The phenotypic hallmark of FAP is the presence of more than 100 colorectal adenomas in combination with extracolonic manifestations.
There is a subset of APC mutation carriers with fewer colorectal adenomas, and, except for desmoid tumours, lacking extradigestive manifestations. This variant disease has been initially referred to as "attenuated adenomatous polyposis coli" (AAPC) then included in a clinical entity called "attenuated familial adenomatous polyposis" (AFAP).
In 2003, a genetically distinct type of AFAP has been identified, called MAP for MUTYH-associated polyposis (MIM 608456). The phenotype is very similar to that of AAPC, but the mode of inheritance is more complicated as bi-allelic mutations are frequent and mono-allelic mutations often asymptomatic [Kairupan & Scott, 2007; Poulsen & Bisgaard, 2008; Shinmura et al. 2012]. Specific guidelines for genetic testing have been proposed for the MUTYH gene [Buecher et al, 2012; Aretz et al, 2013]. MAP is much more frequent than FAP as mutations are found in approximately 20% of attenuated adenomatous polyposis patients, including sporadic cases. Guidelines for surveillance and treatment largely differ from that proposed in FAP and the knowledge of the exact mutation in case of adenomatous polyposis is of most importance to apply the right protocol [Vasen et al, 2008; Buecher et al, 2012; http://www.e-cancer.fr/publications/71-soins/609-summary-of-report-on-polyposis-associated-with-mutyh-biallelic-mutations).
Supported by the French national cancer institute INCa, the French network of nine laboratories involved in MAP genetic testing collected their clinic, histological and molecular data regarding all MUTYH variations identified since 2003. This joint venture enabled to detail the mechanisms of large genomic rearrangements, to develop methods searching for splicing anomalies, to study cancer risks associated with validated pathogenic mutations, to elaborate the the guidelines for surveillance and treatment.
Publications of the French network involved in MUTYH genetic testing
- APC, MYH, and the correlation genotype-phenotype in colorectal polyposis. Lefevre JH, Parc Y, Svrcek M, Kernéis S, Colas C, Shields C, Flejou JF, Parc R, Tiret E. Ann Surg Oncol. 2009 Apr;16(4):871-7. doi: 10.1245/s10434-008-0297-0.
- Colorectal adenomatous polyposis Associated with MYH mutations: genotype and phenotype characteristics. Bouguen G, Manfredi S, Blayau M, Dugast C, Buecher B, Bonneau D, Siproudhis L, David V, Bretagne JF. Dis Colon Rectum. 2007 Oct;50(10):1612-7.
- First large rearrangement in the MUTYH gene and attenuated familial adenomatous polyposis syndrome. Rouleau E, Zattara H, Lefol C, Noguchi T, Briaux A, Buecher B, Bourdon V, Sobol H, Lidereau R, Olschwang S. Clin Genet. 2011 Sep;80(3):301-3. doi: 10.1111/j.1399-0004.2011.01699.x.
- French experts report on MUTYH-associated polyposis (MAP).Buecher B, Bonaïti C, Buisine MP, Colas C, Saurin JC. Fam Cancer. 2012 Sep;11(3):321-8. doi: 10.1007/s10689-012-9511-0.
- Frequent mutation in North African patients with MUTYH-associated polyposis. Lefevre JH, Colas C, Coulet F, Baert-Desurmont S, Mongin C, Tiret E, Frebourg T, Soubrier F, Parc Y. Clin Genet. 2011 Oct;80(4):389-93. doi: 10.1111/j.1399-0004.2010.01528.x.
Identification of a patient with atypical MUTYH-associated polyposis through detection of the KRAS c.34G;T mutation in liver metastasis. Buisine MP, Cattan S, Wacrenier A, Leclerc J, Lejeune S. J Clin Oncol. 2013 Mar 20;31(9):e125-7. doi: 10.1200/JCO.2012.44.7391.
Leiden Open Variation Database of the MUTYH gene. Out AA, Tops CM, Nielsen M, Weiss MM, van Minderhout IJ, Fokkema IF, Buisine MP, Claes K, Colas C, Fodde R, Fostira F, Franken PF, Gaustadnes M, Heinimann K, Hodgson SV, Hogervorst FB, Holinski-Feder E, Lagerstedt-Robinson K, Olschwang S, van den Ouweland AM, Redeker EJ, Scott RJ, Vankeirsbilck B, Grønlund RV, Wijnen JT, Wikman FP, Aretz S, Sampson JR, Devilee P, den Dunnen JT, Hes FJ. Hum Mutat. 2010 Nov;31(11):1205-15. doi: 10.1002/humu.21343.
MYH biallelic mutation can inactivate the two genetic pathways of colorectal cancer by APC or MLH1 transversions. Lefevre JH, Colas C, Coulet F, Bonilla C, Mourra N, Flejou JF, Tiret E, Bodmer W, Soubrier F, Parc Y. Fam Cancer. 2010 Dec;9(4):589-94. doi: 10.1007/s10689-010-9367-0.
Similar colorectal cancer risk in patients with monoallelic and biallelic mutations in the MYH gene identified in a population with adenomatous polyposis. Olschwang S, Blanché H, de Moncuit C, Thomas G. Genet Test. 2007 Fall;11(3):315-20.
The first mutations in the MYH gene reported in Moroccan colon cancer patients. Laarabi FZ, Cherkaoui Jaouad I, Baert-Desurmont S, Ouldim K, Ibrahimi A, Kanouni N, Frebourg T, Sefiani A. Gene. 2012 Mar 15;496(1):55-8. doi: 10.1016/j.gene.2011.12.024.
The thorough screening of the MUTYH gene in a large French cohort of sporadic colorectal cancers. Kury S, Buecher B, Robiou-du-Pont S, Scoul C, Colman H, Lelièvre B, Olschwang S, Le Houérou C, Le Neel T, Faroux R, Ollivry J, Lafraise B, Chupin LD, Bézieau S. Genet Test. 2007 Winter;11(4):373-9.
Unexplained polyposis: a challenge for geneticists, pathologists and gastroenterologists. Mongin C, Coulet F, Lefevre JH, Colas C, Svrcek M, Eyries M, Lahely Y, Fléjou JF, Soubrier F, Parc Y. Clin Genet. 2012 Jan;81(1):38-46. doi: 10.1111/j.1399-0004.2011.01676.x.