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MYCN gene overrepresentation detected in primary neuroblastoma tumour cells without amplification
Author(s) -
Valent Alexander,
Le Roux Gwenaëlle,
Barrois Michel,
TerrierLacombe MarieJosé,
ValteauCouanet Dominique,
Léon Bernadette,
Spengler Barbara,
Lenoir Gilbert,
Bénard Jean,
Bernheim Alain
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1244
Subject(s) - neuroblastoma , isochromosome , gene duplication , n myc , biology , cancer research , gene , chromosomal translocation , chromosome 17 (human) , chromosome , oncogene , cancer , karyotype , pathology , medicine , genetics , ganglioneuroma , cell cycle , cell culture
Neuroblastoma is the most frequent solid extracranial neoplasm of childhood, with a median age of presentation of under 2 years. This tumour is highly malignant in patients older than 12 months of age with metastatic disease. Clinical studies have confirmed that amplification of the MYCN proto‐oncogene is one of the best prognostic indicators of poor outcome. Approximately 30% of neuroblastoma tumours present MYCN amplification at diagnosis. Far less is known about the incidence and consequences of overrepresentation of the gene due to duplication or rearrangement of the chromosome arm in which the gene is situated. This study has analysed 110 neuroblastomas by FISH and has detected a gain of 1–3 copies per cell of MYCN in 8% of MYCN ‐non‐amplified tumours. In these primary tumours, cells gained small numbers of additional MYCN genes by two mechanisms: formation of an isochromosome 2p, or an unbalanced translocation involving the short arm of chromosome 2 (with MYCN ) and various partner chromosomes. Quantitative RT‐PCR showed three‐ to seven‐fold elevated MYCN expression in three tumours. Although the follow‐up time to date is still short, clinical outcome suggests that low‐level overexpression of the MYCN gene does not enhance tumour aggressiveness and rapidity of disease progression, as is often seen in neuroblastoma with MYCN amplification. It is hypothesized that the small elevation in MYCN expression could alter the regulation of apoptosis, as has been shown in experimental models. Copyright © 2002 John Wiley & Sons, Ltd.