Phenotype versus genotype in gliomas displaying inter- or intratumoral histological heterogeneity.
OBJECTIVE
Molecular classification of gliomas is becoming increasingly important clinically as an adjunct to histopathological diagnosis. Whereas histological heterogeneity of gliomas is well recognized, less is known of the relationship between histological heterogeneity and genetic alterations. Our objective was to investigate the relationship between genotype and phenotype for markers of potential clinical utility in histologically heterogeneous gliomas.


METHODS
We have used laser capture microdissection to sample the various histological phenotypes present in 42 tumors from 25 glioma cases with either inter- or intratumoral histological heterogeneity, and multiple simultaneous PCR amplification of microsatellite markers and capillary electrophoresis to determine allelic imbalance in chromosomes 1p, 19q, 17p, 10p, and 10q.


RESULTS
Loss of 1p36 and 19q13 was seen only in oligodendroglial histology in 7 of 13 oligodendrogliomas. 17p13 loss was found in 14 of 41 tumors in astrocytic, oligoastrocytic, oligodendroglial, and glioblastomatous histologies. Chromosome 10 loss was seen in all of the high-grade histologies in 7 of 7 glioblastomas with an oligodendroglial component and in 1 of 5 low-grade oligodendroglial regions present within high-grade tumors. Seven tumors from 5 cases had no detectable losses of any markers investigated. In 13 tumors with intratumoral heterogeneity, identical genetic losses were present in all areas of histological differentiation. Additional losses were seen in some but not all of the histologies within 2 tumors and were associated with progression in 3 cases.


CONCLUSIONS
The gliomas in this study were more homogeneous in their genotype than their histological phenotype with regions of differing histological subtype indistinguishable by the genetic markers investigated, supporting a monoclonal origin of these tumors.
Walker
Carol
C
Clatterbridge Cancer Research Trust, J. K. Douglas Laboratories, Clatterbridge Hospital, Bebington, Wirral, CH63 4JY United Kingdom. carolw@ccrt.co.uk
du Plessis
Daniel G
DG
Joyce
Kathy A
KA
Machell
Yvonne
Y
Thomson-Hehir
Joanne
J
Al Haddad
Syed A
SA
Broome
John C
JC
Warnke
Peter C
PC
D000483:Alleles; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002886:Chromosomes, Human, Pair 17; D002888:Chromosomes, Human, Pair 19; D018450:Disease Progression; D016158:Genes, p53; D005819:Genetic Markers; D005838:Genotype; D005910:Glioma / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D007834:Lasers; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D010641:Phenotype
D014408:Biomarkers, Tumor; D005819:Genetic Markers