Alternative pathways of MYCN gene copy number increase in primary neuroblastoma tumors.
Neuroblastomas, tumors of the sympathetic nervous system, account for 7-10% of the cancers of childhood. Genetic studies have shown, and this study has confirmed, that neuroblastomas are very heterogeneous; no single genetic change common to all neuroblastomas has yet been identified. One genetic aberration found frequently in this pediatric tumor is MYCN gene amplification. Recently we identified a new subset of tumors showing MYCN gain (small increases in gene number arising from unbalanced translocation). To investigate whether gain precedes amplification or is an independent event, we surveyed 200 primary tumors for MYCN copy number with fluorescence in situ hybridization; 152 of 200 (76%) were MYCN single-copy tumors, whereas 48 of 200 (24%) tumors harbored MYCN abnormalities: 36 of the 48 (75%) had MYCN amplification and 12 (25%) had MYCN gain. Among the 36 with MYCN amplified gene, we found four that also showed gain. In three tumors exhibiting simultaneous gain and amplification, these two events were detected in neighboring cells. In the fourth case we detected only MYCN gain in metastatic neuroblasts in the bone marrow, but both MYCN amplification and gain in the primary tumor. The detailed study of these four cases suggests that there may be several different mechanisms leading to increase in MYCN copy number. Further studies in other human malignancies are necessary to determine whether simultaneous gain and amplification are specific to neuroblastoma or constitute a general mechanism by which tumor cells can acquire selective growth advantage.
Valent
Alexander
A
Laboratoire de Génomique Cellulaire des Cancers, Institut Gustave Roussy, Unité Mixte de Recherche 8125, Centre National de la Recherche Scientifique, rue Camille Desmoulins 39, 94805 Villejuif Cedex, France. avalent@igr.fr
Guillaud-Bataille
Marine
M
Farra
Chantal
C
Lozach
François
F
Spengler
Barbara
B
Terrier-Lacombe
Marie-José
MJ
Valteau-Couanet
Dominique
D
Danglot
Gisèle
G
Lenoir
Gilbert M
GM
Brison
Olivier
O
Bénard
Jean
J
Bernheim
Alain
A
D002648:Child; D002999:Clone Cells / Q000473:pathology; D005784:Gene Amplification; D016259:Genes, myc; D018740:Genetic Heterogeneity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008957:Models, Genetic; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology