Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma Journal Article

   

Authors:	Lavarino, C.; Cheung, N. K. V.; Garcia, I.; Domenech, G.; de Torres, C.; Alaminos, M.; Rios, J.; Gerald, W. L.; Kushner, B.; Laquaglia, M.; Mora, J.
Article Title:	Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma
Abstract:	Background: Neuroblastoma (NB) tumours have the highest incidence of spontaneous remission, especially among the stage 4s NB subgroup affecting infants. Clinical distinction of stage 4s from lethal stage 4 can be difficult, but critical for therapeutic decisions. The aim of this study was to investigate chromosomal alterations and differential gene expression amongst infant disseminated NB subgroups. Methods: Thirty-five NB tumours from patients diagnosed at < 18 months (25 stage 4 and 10 stage 4s), were evaluated by allelic and gene expression analyses. Results: All stage 4s patients underwent spontaneous remission, only 48% stage 4 patients survived despite combined modality therapy. Stage 4 tumours were 90% near-diploid/tetraploid, 44% MYCN amplified, 77% had 1p LOH (50% 1p36), 23% 11q and/or 14q LOH (27%) and 47% had 17q gain. Stage 4s were 90% near-triploid, none MYCN amplified and LOH was restricted to 11q. Initial comparison analyses between stage 4s and 4 < 12 months tumours revealed distinct gene expression profiles. A significant portion of genes mapped to chromosome 1 (P < 0.0001), 90% with higher expression in stage 4s, and chromosome 11 (P = 0.0054), 91% with higher expression in stage 4. Less definite expression profiles were observed between stage 4s and 4 < 18m, yet, association with chromosomes 1 (P < 0.0001) and 11 (P = 0.005) was maintained. Distinct gene expression profiles but no significant association with specific chromosomal region localization was observed between stage 4s and stage 4 < 18 months without MYCN amplification. Conclusion: Specific chromosomal aberrations are associated with distinct gene expression profiles which characterize spontaneously regressing or aggressive infant NB, providing the biological basis for the distinct clinical behaviour. © 2009 Lavarino et al; licensee BioMed Central Ltd.
Keywords:	cancer survival; clinical article; controlled study; human tissue; unclassified drug; genetics; pathogenesis; doxorubicin; cancer combination chemotherapy; cancer staging; neoplasm staging; chromosome 1; allele; carboplatin; gene amplification; gene expression profiling; etoposide; genetic association; genetic variability; cyclophosphamide; pathology; tumor marker; childhood cancer; gene expression regulation; chromosome aberration; gene mapping; gene expression regulation, neoplastic; cancer regression; infant; neuroblastoma; chromosome aberrations; chromosome analysis; chromosome 11; tetraploidy; protein mycn; chromosome 17q; diploidy; oncogenesis and malignant transformation; neoplastic processes
Journal Title:	BMC Cancer
Volume:	9
ISSN:	1471-2407
Publisher:	Biomed Central Ltd
Date Published:	2009-02-03
Start Page:	44
Language:	English
DOI:	10.1186/1471-2407-9-44
PUBMED:	19192278
PROVIDER:	scopus
PMCID:	PMC2642835
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-60949083060&partnerID=40&md5=a6142b0fce03c818fb4962a11a6d447a
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "Art. No.: 44" - "CODEN: BCMAC" - "Source: Scopus"

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