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Loss of Heterozygosity Analysis of Chromosomes 9, 10 and 17 in Gliomas in Families

Published online by Cambridge University Press:  18 September 2015

Christopher J. Watling ,
Donald J. van Meyel ,
David A. Ramsay ,
David R. Macdonald  and
J. Gregory Cairncross
Christopher J. Watling
Affiliation:
Department of Clinical Neurological Sciences, University of Western Ontario and the London Regional Cancer Centre, London
Donald J. van Meyel
Affiliation:
Department of Microbiology and Immunology, University of Western Ontario and the London Regional Cancer Centre, London Department of Oncology, University of Western Ontario and the London Regional Cancer Centre, London
David A. Ramsay
Affiliation:
Department of Clinical Neurological Sciences, University of Western Ontario and the London Regional Cancer Centre, London Department of Pathology, University of Western Ontario and the London Regional Cancer Centre, London
David R. Macdonald
Affiliation:
Department of Clinical Neurological Sciences, University of Western Ontario and the London Regional Cancer Centre, London Department of Oncology, University of Western Ontario and the London Regional Cancer Centre, London
J. Gregory Cairncross*
Affiliation:
Department of Clinical Neurological Sciences, University of Western Ontario and the London Regional Cancer Centre, London Department of Microbiology and Immunology, University of Western Ontario and the London Regional Cancer Centre, London Department of Oncology, University of Western Ontario and the London Regional Cancer Centre, London
*
London Regional Cancer Centre, 790 Commissioners Road East, London, Ontario, Canada N6A 4L6
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Abstract:

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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.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 22 , Issue 1 , February 1995 , pp. 17 - 21
Copyright
Copyright © Canadian Neurological Sciences Federation 1995

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