Loss of Heterozygosity Analysis of Chromosomes 9, 10 and 17
in Gliomas in Families
Christopher J Watling, Donald J van Meyel, David A Ramsay,
David R Macdonald and J Gregory Cairncross
Abstract:
Background: Studies of sporadic malignant
gliomas have identified structural abnormalities in a number
of chromosomal regions, especially losses of DNA on 9p, 10 and
17p. Purpose: We undertook the following molecular
analysis in families with glioma to determine the frequency
of chromosomal losses in these regions and to test the utility
of microsatellite markers in demonstrating losses of heterozygosity.
Methods: Genomic DNA was extracted from tumor
tissue and venous blood from 20 patients with a family history
of glioma. Dinucleotide repeat polymorphisms (microsatellites)
were analyzed by polymerase chain reaction to assess loss of
constitutional heterozygosity (LOH) on 9p, 10 and 17p. Three
polymorphic markers on chromosome 9 (D9S104, D9S161, D9S165),
one on chromosome 10 (D10S209), and two on 17p (D17S786, D17S796)
were used. Autoradiographic films were analyzed for LOH after
radioactively labelled polymerase chain reaction products were
resolved on denaturing formamide-acrylamide gels. Results:
Of 20 patients informative for at least one of three chromosome
9 markers, 12 (60%) showed LOH at one or more loci; of 9 informative
for the chromosome 10 marker, 4 (44%) showed LOH; and of 16
informative for at least one of two chromosome 17 markers, 7
(44%) showed LOH at one or both loci. These LOH rates do not
include instances of tumor nullizygosity (0 - 35%) and therefore
represent minimum frequencies of chromosomal losses at these
loci. Conclusions: Microsatellite markers can
be used to detect LOH in archival glioma tissue. As in sporadic
gliomas, frequent LOH was observed on 9p (9p21-22), 10 and 17p,
supporting the notion that these regions may harbour tumor suppressor
genes important in glioma development. Further work will be
required to determine whether the proportion of LOH in these
chromosomal regions is higher in familial gliomas than sporadic
ones, as might occur with an inherited suppressor gene conferring
susceptibility to gliomas in families.
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Can.
J. Neurol. Sci. 1995; 22: 17-21
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