Association of chromosome 7, chromosome 10 and EGFR gene amplification in glioblastoma multiforme.
Glioblastoma multiforme (GBM) is characterized by intratumoral heterogeneity in both histomorphological and genetic changes, displaying a wide variety of numerical chromosome aberrations, the most common of which are trisomy 7 and monosomy 10. The amplification of the epidermal growth factor receptor (EGFR) gene is the most frequently reported genetic abnormality. The associations between these parameters and their implication in the tumoral progression are poorly understood. We performed simultaneous fluorescence in situ hybridization (FISH) with centromeric DNA probes for chromosomes 7 and 10 in smear preparations, and EGFR gene amplification by PCR from 25 cases of GBM. Trisomy/ polysomy for chromosome 7 was present in 76% of cases and monosomy 10 in 68%. Both alterations were associated in 56% of cases. The EGFR gene was amplified in 52% of tumors; in 44% associated with trisomy/ polysomy 7, and in 36% with monosomy 10. The three parameters were associated together in 28% of cases. Kaplan-Meier survival rate analysis demonstrated lower survival rates in patients with monosomy 10, trisomy 7, and monosomy associated with trisomy 7. The other combinations were not different in frequency in relation to survival. In the present study, trisomy/polysomy 7 and monosomy 10 have been found to be frequently associated. The combination of both anomalies is probably important in the tumorigenesis of glioblastoma. Moreover, this association is apparently independent of EGFR gene amplification, which could be a later event in this process.
Lopez-Gines
C
C
Department of Pathology, Medical School, University of Valencia, Spain. concha.lopez@uv.es
Cerda-Nicolas
M
M
Gil-Benso
R
R
Pellin
A
A
Lopez-Guerrero
J A
JA
Callaghan
R
R
Benito
R
R
Roldan
P
P
Piquer
J
J
Llacer
J
J
Barbera
J
J
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002648:Child; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D066246:ErbB Receptors