|
|
Molecular Genetic Study
of a Metastatic Oligodendroglioma
M.T.
Giordana, C. Ghimenti, E. Leonardo, I. Balteri, M. Iudicello, D. Duò
Department
of Neuroscience, University of Turin, Turin, Italy
Extracranial
spread of neuroectodermal tumors is an unusual event, most frequently expected
from glioblastomas and medulloblastomas.
Single cases of metastatic oligodendrogliomas have been described, but no
genetic data are reported.
Oligodendrogliomas
are characterized by distinct genetic alterations, i.e. loss of hetero-zygosity
(LOH) of 1p and 19q; therefore, molecular genetic analysis of metastatic cases
is of considerable interest.
It may be instrumental in defining the distant tumor as metastatic
oligodendroglioma and give clues to the genetic events associated with the
highly malignant transformation.
We
present the case of a patient with multiple bone metastases from a cerebral
oligodendroglioma.
Oligodendroglioma grade II was the diagnosis both at original and second
operation, performed 7 and 1 years before the extracranial dissemination.
The extraneural spread presented before the local intracranial recurrence.
The patient received procarbazine, lomustine, vincristine chemotherapy and
radiotherapy after the second surgery.
The computed tomography-guided biopsy of the bone lesions revealed tumor cells
positive for GFAP, S-100 and Leu-7 and negative for cytokeratin, LCA and
EMA.
The genetic analysis of DNA from the original tumor, the bone metastasis and the
autoptic brain tumor showed LOH of 1p; heterozygous deletion of CDKN2A/p16 was
detected as additional alteration in the metastasis and in the intracranial
tumor at autopsy.
TP53, MDM2 and CDKN2A/p14ARF genes were unchanged.
Repeated brain surgery and extended survival may have acted as promoter of
extraneural dissemination.
Loss of CDKN2A most probably played an important role in the malignant
progression; its involvement in metastatic potential remains to be
clarified.
Our data confirm that malignant transformation of oliogodendrogliomas may be
undetected by histology and underscore the importance of genetic analysis.
Coincidentally with intensive anticancer therapy, chemotherapy included,
employed in patients with oligodendroglioma and the ensuing long survival, the
frequency of metastatic oliogodendrogliomas may increase.
Keywords: CDKN2A deletion, genetic analysis, LOH 1p/19q,
oligodendroglioma metastatic
Copyright
© 2004 Kluwer
Academic Publishers. All
rights reserved
Source: http://www.kluweronline.com/article.asp?J=5042&I=109&A=7
|
