|
|
Molecular Genetic Aspects of
Oligodendrogliomas Including Analysis by Comparative Genomic
Hybridization
Sandra H. Bigner,
Mark R. Matthews, B. K. A. Rasheed, Rodney
N. Wiltshire, Henry S. Friedman, Allan H.
Friedman, Timothy T. Stenzel, Donald M.
Dawes, Roger E. McLendon and Darell D.
Bigner
From the Departments of Pathology
[S.H.B., M.R.M., B.K.A.R., R.N.W., T.T.S., D.M.D,. R.E.M., D.D.B..],
Pediatrics [H.S.F.], and Surgery [A.H.F.], Duke University Medical
Center, Durham, North Carolina. Address reprint requests to Dr. Sandra
H. Bigner, Department of Pathology, Box 3712, Duke
University Medical Center, Durham, NC 27710. E-mail:
mailto:bigne002@mc.duke.edu . Accepted for publication April 13, 1999.
Oligodendroglial neoplasms are a
subgroup of gliomas with distinctive morphological
characteristics.
In the present study we have evaluated
a series of these tumors to define their molecular profiles and
to determine whether there is a relationship between molecular
genetic parameters and histological pattern in this tumor
type.
Loss of heterozygosity (LOH)
for 1p and 19q was seen in 17/23 (74%) well-differentiated oligodendrogliomas,
in 18/23 (83%) anaplastic oligodendrogliomas, and in 3/8
(38%) oligoastrocytomas grades II and III.
LOH for 17p and/or mutations of
the TP53 gene occurred in 14 of these 55
tumors.
Only one of the 14 cases with 17p LOH/TP53
gene mutation also had LOH for 1p and 19q, and significant
astrocytic elements were seen histologically in the
majority of these 14 tumors.
LOH for 9p and/or deletion of
the CDKN2A gene occurred in 15 of these 55 tumors, and 11
of these cases were among the 24 (42%) anaplastic oligodendrogliomas.
Comparative genomic hybridization (CGH)
identified the majority of cases with 1p and 19q loss and,
in addition, showed frequent loss of chromosomes 4, 14, 15,
and 18.
These findings demonstrate that
oligodendroglial neoplasms usually have loss of 1p and 19q
whereas astrocytomas of the progressive type frequently
contain mutations of the TP53 gene, and that 9p loss
and CDKN2A deletions are associated with progression from
well-differentiated to anaplastic oligodendrogliomas.
© 1999 American Society for
Investigative Pathology
|