Correspondence

Survival of Patients with Turcot's Syndrome and Glioblastoma

N Engl J Med 1996; 334:736-737March 14, 1996

Article

To the Editor:

Using molecular evidence, Hamilton et al. (March 30 issue)1 defined two germ-line defects associated with Turcot's syndrome, one of which is usually found in hereditary nonpolyposis colorectal cancer, and the other of which is usually found in familial adenomatous polyposis. The former defect is characterized by mutations in mismatch-repair genes, which lead to widespread microsatellite instability. Exceptional survival rates of more than three years have been reported in three patients with glioblastoma linked to the form of Turcot's syndrome characterized by colorectal cancer,1 whereas the expected median survival rate is about eight months.2 Thus, the question arises whether mutations, inherited or acquired, in one of the several characterized mismatch-repair genes may favorably influence the prognosis of patients with glioblastoma. Furthermore, it has been argued that the improved prognosis of patients with hereditary nonpolyposis colorectal cancer may be due to counterbalancing of the high mutational load by selection and increased cell replication or to an enhanced immune response generated by high levels of mutant proteins.3

However, the prognosis of glioblastomas in syndromes associated with hereditary nonpolyposis colorectal cancer may not be generally favorable. We recently found the survival of one patient with sporadic glioblastoma and two patients with familial glioblastoma, which manifested in a manner typical of hereditary nonpolyposis colorectal cancer, to be quite poor. One family had a germ-line mutation at codon 34 in the hMLH1 gene.4 An obligate carrier of the disease allele in the family died at the age of 32 of a glioblastoma that had been diagnosed a few months earlier, and a colorectal carcinoma was found at autopsy. In another sporadic case with the concurrence of a glioblastoma and a colorectal carcinoma, we found instability in five microsatellite markers (dinucleotide cytosine-adenosine–repeat markers) in the visceral neoplasm but not in the glioblastoma. Such heterogeneity of microsatellite instability between tumors was also observed by Hamilton et al.1 This patient survived only a few months. In another family with hereditary nonpolyposis colorectal cancer that harbored a germ-line mutation in the mismatch-repair gene hMSH2 (a deletion of two base pairs at codon 129), a 30-year-old obligate carrier died of glioblastoma one year after diagnosis.4 In contrast to the fatal outcome in the patients with brain tumors, the prognosis of colorectal carcinomas was highly variable in these families (range of survival, 1 to 12 years; median, 5). It appears that the clinical course of glioblastomas in patients with the mismatch-repair–deficient form of Turcot's syndrome can vary.

Adrian Merlo, M.D.
Christoph Rochlitz, M.D.
Rodney Scott, Ph.D.
University of Basel, CH-4031 Basel, Switzerland

4 References

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   Buerstedde JM, Alday P, Torhorst J, Weber W, Muller H, Scott R. Detection of new mutations in six out of 10 Swiss HNPCC families by genomic sequencing of the hMSH2 and hMLH1 genes. J Med Genet 1995;32:909-912
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Citing Articles (7)

Citing Articles

1. 1

   Eriks A. Lusis, Sarah Travers, Sarah C. Jost, Arie Perry. (2010) Glioblastomas With Giant Cell and Sarcomatous Features in Patients With Turcot Syndrome Type 1. Neurosurgery 67:3, 811-817
   CrossRef

2. 2

   Joachim Baehring, Pei Hui, Joseph Piepmeier, Serguei I. Bannykh. (2009) Anaplastic oligoastrocytoma in Turcot syndrome. Journal of Neuro-Oncology 95:2, 293-298
   CrossRef

3. 3

   Alexander F. Jeans, Ian Frayling, Bharat Jasani, Lucy Side, Claire Blesing, Olaf Ansorge. (2009) Cerebral primitive neuroectodermal tumor in an adult with a heterozygous MSH2 mutation. Nature Reviews Clinical Oncology 6:5, 295-299
   CrossRef

4. 4

   C. Lebrun, S. Olschwang, S. Jeannin, F. Vandenbos, H. Sobol, M. Frenay. (2007) Turcot syndrome confirmed with molecular analysis. European Journal of Neurology 14:4, 470-472
   CrossRef

5. 5

   Takashi Tamiya, Shuji Hamazaki, Yasuhiro Ono, Koji Tokunaga, Kengo Matsumoto, Tomohisa Furuta, Takashi Ohmoto. (2000) Ganglioglioma in a patient with Turcot syndrome. Journal of Neurosurgery 92:1, 170-175
   CrossRef

6. 6

   Erwin Van Meir. (1998) Turcot's syndrome: Phenotype of brain tumors, survival and mode of inheritance. International Journal of Cancer 75:1, 162-164
   CrossRef

7. 7

   Karl Heinimann, Hansjakob Müller, Walter Weber, Rodney J. Scott. (1997) Disease expression in Swiss hereditary non-polyposis colorectal cancer (HNPCC) kindreds. International Journal of Cancer 74:3, 281-285
   CrossRef