Meningiomas: loss of heterozygosity on chromosome 10 and marker-specific correlations with grade, recurrence, and survival.
OBJECTIVE
In a study of 208 meningiomas, we found a high incidence of loss of heterozygosity (LOH) on chromosome 10 in benign (73.4%), atypical (80.0%), and malignant (86.7%) tumors. A large percentage of the benign and atypical tumors and an increasing percentage of malignant tumors had LOH on multiple loci (43.9%, 45%, and 66.7%, respectively). The high incidence of LOH occurring early in meningioma progression suggests that LOH at individual alleles may serve as a marker of clinically relevant alterations useful for patient diagnosis, the subclassification of tumors, and/or the treatment of patients.


METHODS
To test this, we examined 208 sporadic and recurrent meningiomas of all grades for correlations between LOH at 11 markers on chromosome 10 and tumor location, histology, and grade and patient race, gender, age, recurrence, and survival.


RESULTS
Several significant correlations were found. The data indicate that genetic differences occur not only between tumors of different grade, but also between tumors of the same grade, and therefore may be useful to define genetic subsets with clinical implications. LOH at D10S179 (P = 0.001) or D10S169 (P = 0.004) is most likely present in higher-grade meningiomas and, when present in benign tumors, may signify sampling error or a morphologically benign but biologically aggressive tumor. Furthermore, LOH at D10S209 (P = 0.06) and D10S169 (P = 0.01) may predict shorter survival and/or higher rates of recurrence, respectively, in tumors with benign or malignant histology.


CONCLUSIONS
We conclude that these chromosome 10 markers deserve further testing as unfavorable prognostic indicators for meningioma patients.
Mihaila
Dana
D
Hermelin Brain Tumor Center, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
Jankowski
Michelle
M
Gutiérrez
Jorge A
JA
Rosenblum
Mark L
ML
Newsham
Irene F
IF
Bögler
Oliver
O
Rempel
Sandra A
SA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008577:Meningeal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008579:Meningioma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D018895:Microsatellite Repeats; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate
D004273:DNA, Neoplasm; D005819:Genetic Markers