Loss of heterozygosity of TRIM3 in malignant gliomas.
BACKGROUND
Malignant gliomas are frequent primary brain tumors associated with poor prognosis and very limited response to conventional chemo- and radio-therapies. Besides sharing common growth features with other types of solid tumors, gliomas are highly invasive into adjacent brain tissue, which renders them particularly aggressive and their surgical resection inefficient. Therefore, insights into glioma formation are of fundamental interest in order to provide novel molecular targets for diagnostic purposes and potential anti-cancer drugs. Human Tripartite motif protein 3 (TRIM3) encodes a structural homolog of Drosophila brain tumor (brat) implicated in progenitor cell proliferation control and cancer stem cell suppression. TRIM3 is located within the loss of allelic heterozygosity (LOH) hotspot of chromosome segment 11p15.5, indicating a potential role in tumor suppression.


METHODS
Here we analyze 70 primary human gliomas of all types and grades and report somatic deletion mapping as well as single nucleotide polymorphism analysis together with quantitative real-time PCR of chromosome segment 11p15.5.


RESULTS
Our analysis identifies LOH in 17 cases (24%) of primary human glioma which defines a common 130 kb-wide interval within the TRIM3 locus as a minimal area of loss. We further detect altered genomic dosage of TRIM3 in two glioma cases with LOH at 11p15.5, indicating homozygous deletions of TRIM3.


CONCLUSIONS
Loss of heterozygosity of chromosome segment 11p15.5 in malignant gliomas suggests TRIM3 as a candidate brain tumor suppressor gene.
Boulay
Jean-Louis
JL
Department of Biomedicine, University Hospital, Basel, Switzerland. Jean-Louis.Boulay@unibas.ch
Stiefel
Urs
U
Taylor
Elisabeth
E
Dolder
Béatrice
B
Merlo
Adrian
A
Hirth
Frank
F
D001932:Brain Neoplasms / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016324:Sequence Tagged Sites
D002352:Carrier Proteins; C426543:TRIM3 protein, human