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Turcot syndrome

Written2005-08Maria Cristina Digilio
Medical Genetics, Bambino Gesù Hospital, Piazza S. Onofrio 4, 00165ù Rome, Italy

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Other namesMalignant tumors of the central nervous system associated with familial polyposis of the colon
Atlas_Id 10026
Genes implicated inAPC   MLH1   MHS6   MSH2   PMS2  
Note Turcot syndrome (TS) is characterized by the association of colonic polyps and central nervous system tumors. The relative risk of cerebral tumor in patients with familial adenomatous polyposis is considered 92 times more that found in the general population. The predominant brain tumors are medulloblastoma and gliomas.
Inheritance Both autosomal dominant and autosomal recessive modes of inheritance have been described, based on the analysis of familial segregation of the disease and the results of molecular studies. Nevertheless, considering the low penetrance and rarity of TS, the involvement of a major gene in association with a second locus containing a modifier gene or of environmenmtal factors has been suggested.


Neoplastic risk Cardinal findings in TS are colonic polyps with tendency to colorectal cancer and malignant central nervous system tumors.
  • Colonic polyps: Three types of polyposis coli are described to occur in TS: 1) Type 1 is characterized by multiple colonic polyps numbering between 20 and 100, some of which may exceed 3 cm in diameter; 2) Type 2 is characterizd by a small number of colonic polyps, usually less than 10; 3) Type 3 is characterized by numerous small colonic polyps similar to those of classical familial polyposys coli. Based on molecular entities, two groups can differentiated: the one due to mutation in the APC gene (see below), characterized by colonic polyps, the second one due to mutations in the DNA mismatch repair (MMR) genes (see below) and characterized by colorectal adenomas without polyposis.
  • Colorectal cancer: the polyps frequently show malignant transformation in the second and third decades of life.
  • Central nervous system tumors: Two major types of TS are distinguished based on different types of central nervous system tumors. The first one is characterized by childhood cerebellar medullobastoma and the second by gliomas, particularly glioblastoma multiforme, arising in both children and adult. The two different types are related to different molecular pathogenesis. In fact, the first type is caused by mutations in the APC gene (see below), whereas the second type is related to MMR genes mutations (see below).
  • Other: In some instances, patients with TS have additional symptoms characteristic of other genetic conditions with familial polyposis of the coli, including pigmented ocular fundus lesions, epidermal inclusion cysts, osteosclerotic jaw lesions, cafe-au-lait spots or lipomas.
  • Cytogenetics

    Note Chromosome analysis is generally normal in patients with TS

    Genes involved and Proteins

    Gene NameAPC (adenomatous polyposis coli)
    Location 5q22.2
    Note The APC locus consists of 15 exons

    Gene NameMLH1 (human mutL homolog 1)
    Location 3p22.2
    Note The MLH1 locus encompasses approximately 100 kb and consists of 19 exons

    Gene NamePMS2 (PMS1 homolog 2, mismatch repair system component)
    Location 7p22.1
    Note The PMS2 locus encompasses 16 kb and consists of 15 exons
  • APC: APC seems to be invoved in cell adhesion with a role in the beta-catenin-APC interaction. It is possible that the APC complex regulates transmission of the contact inhibition signal into the cells, since APC mutations are associated with the development of hyperplasia, an early event in tumorigenesis. Alternatively, it is possible that the APC-catenin complex regulates adhesions, since loss of cadherin-mediated adhesion can contribute to metastasis
  • MMR genes: MLH1 and PMS2 are involved in DNA mismatch repair, and neoplasms of affected patients show DNA replication errros.
  • Mutations
    Note Germline APC mutations are detectable in 2/3 of patients with TS. In the remaining patients, germline mutations in MMR genes can be found. Molecular analysis have shown that heterozygous, homozygous or compound heterozygous mutations may be implicated in TS. TS caused by APC mutations is associated with childhood cerebellar medulloblastoma and colonic polyps, while TS related to MMR genes is associated with glioma and colorectal adenomas without polyposis. Nevertheless, there is a wide clinical heterogeneity among carriers of mutations in the same gene, and even among pedigrees segregating for the same molecular defect. Such variations could be accounted for by genetic or environmental modifiers. PMS2 mutations have been identified in a few families so far, and a very severe phenotype has been described in most of the cases.


    The glioma-polyposis syndrome.
    Baughman FA Jr, List CF, Williams JR, Muldoon JP, Segarra JM, Volkel JS
    The New England journal of medicine. 1969 ; 281 (24) : 1345-1346.
    PMID 4311244
    Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome.
    Chan TL, Yuen ST, Chung LP, Ho JW, Kwan K, Fan YW, Chan AS, Leung SY
    Genes, chromosomes & cancer. 1999 ; 25 (2) : 75-81.
    PMID 10337989
    Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene.
    De Rosa M, Fasano C, Panariello L, Scarano MI, Belli G, Iannelli A, Ciciliano F, Izzo P
    Oncogene. 2000 ; 19 (13) : 1719-1723.
    PMID 10763829
    Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome.
    De Vos M, Hayward BE, Picton S, Sheridan E, Bonthron DT
    American journal of human genetics. 2004 ; 74 (5) : 954-964.
    PMID 15077197
    The molecular basis of Turcot's syndrome.
    Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B
    The New England journal of medicine. 1995 ; 332 (13) : 839-847.
    PMID 7661930
    Turcot syndrome and its characteristic colonic manifestations.
    Itoh H, Ohsato K
    Diseases of the colon and rectum. 1985 ; 28 (6) : 399-402.
    PMID 4006635
    Turcot's syndrome: evidence for linkage to the adenomatous polyposis coli (APC) locus.
    Lasser DM, DeVivo DC, Garvin J, Wilhelmsen KC
    Neurology. 1994 ; 44 (6) : 1083-1086.
    PMID 8208405
    Turcot's syndrome. Evidence for autosomal dominant inheritance.
    Lewis JH, Ginsberg AL, Toomey KE
    Cancer. 1983 ; 51 (3) : 524-528.
    PMID 6821830
    Hereditary nonpolyposis colorectal cancer and related conditions.
    Lucci-Cordisco E, Zito I, Gensini F, Genuardi M
    American journal of medical genetics. Part A. 2003 ; 122 (4) : 325-334.
    PMID 14518071
    Drastic genetic instability of tumors and normal tissues in Turcot syndrome.
    Miyaki M, Nishio J, Konishi M, Kikuchi-Yanoshita R, Tanaka K, Muraoka M, Nagato M, Chong JM, Koike M, Terada T, Kawahara Y, Fukutome A, Tomiyama J, Chuganji Y, Momoi M, Utsunomiya J
    Oncogene. 1997 ; 15 (23) : 2877-2881.
    PMID 9419979
    Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases.
    Diseases of the colon and rectum. 1959 ; 2 : 465-468.
    PMID 13839882


    This paper should be referenced as such :
    Digilio, MC
    Turcot syndrome
    Atlas Genet Cytogenet Oncol Haematol. 2006;10(1):38-39.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 3 ]

    Genes APC ASCL1 MSH6

    External links

    OrphanetTurcot syndrome with polyposis
    Other databaseTurcot syndrome (GARD)
    Genes implicated inAPC   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inMLH1   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inMHS6   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inMSH2   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  
    Genes implicated inPMS2   [ Atlas ]   [ Entrez ]  [ LOVD ]  [ GeneReviews ]  

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