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Correlation
between genetic alterations and growth of human malignant glioma xenografted in
nude mice
Leuraud P, Taillandier L, Aguirre-Cruz L, Medioni J, Criniere E, Marie Y,
Dutrillaux AM, Kujas M, Duprez A, Delattre JY, Poupon MF, Sanson M
INSERM U495,
Laboratoire de Biologie des Interactions Neurones-Glie, Groupe hospitalier
Pitie-Salpetriere AP-HP, Paris, France; 5FRE 2485 CNRS, Institut Curie, Paris,
France.
In order to develop
preclinical models of malignant astrocytomas and oligodendrogliomas, a series of
54 resected gliomas (37 from oligodendroglial lineage and 17 from astrocytic
lineage) were xenografted subcutaneously into nude mice.
Molecular alterations commonly observed in gliomas subtypes, including LOH 1p
and 1q, LOH 19q, LOH 10p and 10q, LOH 9p, TP53 and PTEN mutations, EGFR
amplification, CDKN2A homozygous deletion and telomerase reactivation were
systematically screened in the original and xenografted tumours.
In all, 23 gliomas grew in nude mice.
The most anaplastic tumours were selected as shown by pathological and molecular
studies of the original tumour as well as shorter survival in patients whose
tumours were successfully grafted.
Comparison between the two growth profiles showed that 10q LOH and EGFR
amplification gave a tumorigenic advantage.
With a few exceptions, the genetic pattern was remarkably stable before and
after growth in nude mice.
These results suggest that subcutaneous xenografts are useful and reproducible
models to analyse the molecular profile of malignant astrocytoma and
oligodendroglioma.
This represents the first step to improve our understanding of the correlations
between molecular alterations and response to standard or experimental
therapies.
PMID: 14676814 [PubMed - in process]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14676814&dopt=Abstract
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