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Turcot syndrome

Thursday 8 April 2004

Definition: The Turcot syndrome is defined by development of colorectal carcinomas and adenomas and primary central nervous system tumors.


- APC-associated Turcot syndrome
- MMR-associated Turcot syndrome (MSI-associated Turcot syndrome)


In one series, two-thirds of the brain tumors seen were medulloblastomas but other studies report the occurrence as closer to one-third.

Medulloblastomas tend to arise in younger patients and are usually associated with familial adenomatous polyposis (FAP).

Adenomas usually develop in the second decade of life. It is typical for hundreds or thousands of polyps to develop. Nearly all cases will eventually progress into colon cancer, most by the age of 40.

Adenomas also develop in the upper GI tract with nearly all patients developing duodenal adenomas sometime in their life. Fundic gland polyps are also characteristic of FAP.


Eighty percent (80%) of FAP cases have a germ-line mutation, usually a truncation, in the adenomatous polyposis coli (APC) gene located on chromosome 5q21-22. The inheritance pattern is autosomal dominant but 30% of cases appear tomr There is genetic evidence that Turcot Syndrome is not allelic to FAP.

MMR system

Nearly all of the residual Turcot syndrome cases are comprised of hereditary non-polyposis colon cancer (HNPCC) and glioblastomas or astrocytomas.

HNPCC is also autosomal dominant arising from mutations in one of five DNA mismatch repair genes.

The majority of HNPCC cases (50-70%) have mutations in hMSH2 and hMLH1, but mutations also occur in hPMS1, hPMS2 and hMSH6.

Mutations in hPMS2 or hMLH1 have been noted in glioblastomas of two Turcot cases6 and hMSH2 mutations in all three Turcot cases studied by another group.

Ninety-five percent (95%) of HNPCC cases have microsatellite instability caused by errors in mismatch repair as opposed to 15% amongst unselected colon cancers.

Microsatellite instability is also exhibited by gliomas in Turcot’s syndrome. Women with HNPCC, as determined by mutations in mismatch repair genes, also have a higher chance of developing endometrial cancer.

At least 95 cases of Turcot’s Syndrome have been reported in the literature2 with associated brain tumors including: 31 cases with glioblastoma, 31 cases with astrocytoma and 27 cases with medulloblastoma.

Dividing this syndrome in two components according to the presence of FAP versus HNPCC and the type of brain tumors leaves one with the intriguing observation that the original cases described by Turcot were siblings, both with polyps, one with glioblastoma and the other a medulloblastoma.

New candidate genes to consider in Turcot syndrome include the DMBT1 gene or the PTC gene.


- mutations in APC gene (medulloblastoma)
- mutation in the mismatch repair gene MLH1 (MIM.120436) (glioblastoma)
- mutations in the mismatch repair gene MSH2 (MIM.600259) (glioblasoma or supratentorial primitive neuroectodermal tumor (SPNET))


- Paraf F, Jothy S, Van Meir EG. Brain tumor-polyposis syndrome: two genetic diseases? J Clin Oncol. 1997 Jul;15(7):2744-58. PMID: 9215849

- Hampel H, and Peltomaki P. Hereditary Colorectal Cancer: Risk Assessment and Management. Clin Genet 2000;58:89-97.

- Hamada H, Kurimoto M, Endo S, Ogiichi T, Akai T, Takaku A. Turcot’s syndrome presenting with medulloblastoma and familiar adenomatous polyposis: a case report and review of the literature. Acta Neurochir (Wein) 1998;140:631-632.

- Powell SM, Petersen GM, Krush AJ, et al. Molecular diagnosis of familial adenomatous polyposis. N Engl J Med 1993;329:1982-1987.

- Petersen GM. Genetic testing and counseling in familial adenomatous polyposis. Oncology (Huntingt) 1996;10:89-94.

- Tops CMJ, Vasen HFA, van Berge Henegouwen G, Simoons PP, van de Klift HM, van Leeuwen ISJ, Breukel C, Fodde R, den Hartog Jager FCA, Nagengast FM, Griffioen G, Khan PM. Genetic evidence that Turcot syndrome is not allelic to familial adenomatous polyposis. Am J Med Gen 1992;43:888-893.

- Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B, Burger PC, Wood PA, Taqi F, Booker SV, Petersen GM, Offerhaus GJA, Tersmette AC, Giardiello FM, Vogelstein B, Kinzler, KW. The Molecular Basis of Turcot’s Syndrome. N Engl J Med 1995;332:839-847.

- Chan TL, Yuen ST, Chung LP, Ho JWC, Kwan K, Fan YW, Chan ASY, Leung SY. Germline hMSH2 and differential somatic mutations in patients with Turcot’s syndrome. Genes, Chromosomes & Cancer 1999;25:75-81.

- Van Meir EG. Letter in Int J Cancer 1998;75:162-164.

- Turcot J, Despr├ęs, J-P, Pierre FS. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum, 1959;2:465-468.

- Mollenhauer J, Wiemann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus KK, von Deimling A, Poustka A, DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumors. Nature Genet 1997;17:32-39.

- Hahn H, et al. Mutations in the human homolog of Drosophila patched in the nevoid basal-cell-carcinoma syndrome. Cell 1997;85:841-851.