Screening for loss of heterozygosity and microsatellite instability in oligodendrogliomas.
To assess the frequency of loss of heterozygosity (LOH) and microsatellite instability (MI) in oligodendrogliomas, we performed an extensive screening of 16 oligodendrogliomas and nine anaplastic oligodendrogliomas by using 132 microsatellite markers on chromosomes 1 through 12 and 15 through 21. In total, 3,135 loci were examined in 25 tumor samples. Only 33/1,965 (1.7%) of oligodendroglioma (low-grade) and 11/1,070 (1.0%) of anaplastic oligodendroglioma (high-grade) loci exhibited MI. High-frequency LOH regions were identified on chromosome arms 1p (31-73% for oligodendrogliomas and 60-100% for anaplastic oligodendrogliomas) and 19q (23-69% for oligodendrogliomas and 100% for anaplastic oligodendrogliomas). In addition, regions on chromosomes 4, 6, and 11 were found to be lost in 30-80% of both oligodendrogliomas and anaplastic oligodendrogliomas. Increased LOH frequency of chromosome 17 (38-40%) was found only in high-grade oligodendrogliomas. The differences in LOH frequencies between low-grade and high-grade oligodendrogliomas in all loci combined and at three loci (DIS447, DIS226, and DIS252) on chromosome arm 1p were determined to be statistically significant [chi 2(1) = 20.2, P < 0.0001, and Fisher's exact test respective P values: 0.01, 0.03, and 0.02]. Our results provide evidence that microsatellite instability does not play an important role in the development of oligodendrogliomas. Furthermore, high LOH frequency on chromosomes 6 and 11 in addition to that identified previously on chromosomes 1, 19, and 4 suggests that multiple candidate tumor suppressor genes on these chromosomes may underlie the processes of initiation and/or progression in oligodendroglioma tumorigenesis.
Zhu
J J
JJ
Neurosurgical Laboratories and Brain Tumor Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Santarius
T
T
Wu
X
X
Tsong
J
J
Guha
A
A
Wu
J K
JK
Hudson
T J
TJ
Black
P M
PM
D000328:Adult; D000483:Alleles; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009837:Oligodendroglioma / Q000235:genetics*
D004273:DNA, Neoplasm