Correspondence

Malignant Gliomas in Adults

N Engl J Med 2008; 359:1850October 23, 2008

Article

To the Editor:

In their Medical Progress article, Wen and Kesari (July 31 issue)1 review the molecular pathogenesis of gliomas yet do not mention the role that DNA tumor viruses may play in tumor formation. In the same issue, Prins et al.2 provide evidence that strongly supports prior research findings that link cytomegalovirus to glioma. Other DNA viruses, such as JC virus, have been implicated in glioma pathogenesis.3 In this regard, it is also important to note that detection of atypical nuclei and high-proliferation indexes in a brain biopsy led to, in at least one instance, the misdiagnosis of a grade III astrocytoma; subsequent polymerase-chain-reaction studies led to a diagnosis of progressive multifocal leukoencephalopathy related to JC virus.4 Further research is therefore needed to understand the link between DNA viruses and glioma.

Michael A. Meyer, M.D.
University of Buffalo, Buffalo, NY 14215
michaelandrewmeyer@yahoo.com

4 References

1. 1

   Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008;359:492-507[Erratum, N Engl J Med 2008;359:877.]
   Full Text | Web of Science | Medline

2. 2

   Prins RM, Cloughesy TF, Liau LM. Cytomegalovirus immunity after vaccination with autologous glioblastoma lysate. N Engl J Med 2008;359:539-541
   Full Text | Web of Science | Medline

3. 3

   Boldorini R, Pagani E, Car PG, et al. Molecular characterisation of JC virus strains detected in human brain tumours. Pathology 2003;35:248-253
   CrossRef | Web of Science | Medline

4. 4

   Van Assche G, Van Ranst M, Sciot R, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med 2005;353:362-368
   Full Text | Web of Science | Medline

Author/Editor Response

Because of space limitations, our review was largely restricted to information that was strongly supported by data. We agree that the studies regarding the potential role of tumor viruses in the pathogenesis of malignant gliomas are intriguing. However, much more research is required to confirm such a link. Although some studies indicate the presence of cytomegalovirus in malignant gliomas,1 other studies have failed to confirm these findings.2,3 In addition, the detection of viruses such as cytomegalovirus in malignant gliomas may not necessarily indicate that these viruses contributed to the transformation of the tumor. An alternative explanation could be reactivation of virus as a result of immunosuppression related to the tumor, corticosteroids, or chemotherapy.2 With the advent of genomewide analytic tools and the recent advances characterizing the glioblastoma genome,4 we may now be able to address the issue of the presence of infectious agents in human cancer by using newer approaches, such as genomic subtraction technologies.5

Patrick Y. Wen, M.D.
Santosh Kesari, M.D., Ph.D.
Dana–Farber/Brigham and Women's Cancer Center, Boston, MA 02115
pwen@partners.org

5 References

1. 1

   Mitchell DA, Xie W, Schmittling R, et al. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol 2008;10:10-18
   CrossRef | Web of Science | Medline

2. 2

   Lau SK, Chen YY, Chen WG, et al. Lack of association of cytomegalovirus with human brain tumors. Mod Pathol 2005;18:838-843
   CrossRef | Web of Science | Medline

3. 3

   Sabatier J, Uro-Coste E, Pommepuy I, et al. Detection of human cytomegalovirus genome and gene products in central nervous system tumours. Br J Cancer 2005;92:747-750
   CrossRef | Web of Science | Medline

4. 4

   The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008 September 4 (Epub ahead of print).
   

5. 5

   MacConaill L, Meyerson M. Adding pathogens by genomic subtraction. Nat Genet 2008;40:380-382
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   V. L. Jacobs, R. P. Landry, Y. Liu, E. A. Romero-Sandoval, J. A. De Leo. (2011) Propentofylline decreases tumor growth in a rodent model of glioblastoma multiforme by a direct mechanism on microglia. Neuro-Oncology
   CrossRef

2. 2

   Woo-Young Kim, Ho-Young Lee. (2009) Brain angiogenesis in developmental and pathological processes: mechanism and therapeutic intervention in brain tumors. FEBS Journal 276:17, 4653-4664
   CrossRef

3. 3

   Jin-Xiang Cheng, Bo-Lin Liu, Xiang Zhang. (2009) How powerful is CD133 as a cancer stem cell marker in brain tumors?. Cancer Treatment Reviews 35:5, 403-408
   CrossRef