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(American Journal of Pathology. 2001;158:1579-1584.)
© 2001 American Society for Investigative Pathology

Short Communications

In Vivo Elimination of Acentric Double Minutes Containing Amplified MYCN from Neuroblastoma Tumor Cells Through the Formation of Micronuclei

Alexander Valent^*, Jean Bénard, Bernard Clausse, Michel Barrois, Dominique Valteau-Couanet, Marie-José Terrier-Lacombe^¶, Barbara Spengler^|| and Alain Bernheim^*

From the Laboratoire de Génomique Cellulaire des Cancers Centre National de la Recherche Scientifique Unité Mixte de Recherche,^*
the Laboratoire de Cytogénétique,
the Unité des Marqueurs Génétiques des Cancers,
the Département d’Anatomopathologie^¶
and the Département de Pédiatrie,
Institut Gustave Roussy, Villejuif, France; and the Department of Biological Sciences,^||
Fordham University, Bronx, New York

Neuroblastoma, the most common solid extracranial neoplasm in children, shows an appreciable variability in clinical evolution. Amplification of the MYCN oncogene in this tumor is detected in 25 to 30% of cases and is associated with poor clinical outcome. In this study, quantitative polymerase chain reaction and fluorescence in situ hybridization were used to determine MYCN amplification status in 46 neuroblastoma tumors. MYCN amplification was detected in tumors from 11 patients. Fluorescence in situ hybridization revealed the presence of micronuclei containing amplified MYCN sequences in 8 of the 11 tumors. Micronuclei are indicative of spontaneous elimination or loss of amplified sequences by tumor cells. Because the elimination of amplified sequences can be enhanced in vitro by specific drugs such as hydroxyurea, our observations suggest a new therapeutic strategy specifically targeted to cells with amplified genes.

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