Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma
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AuthorLavarino, Cinzia; Cheung, Nai-Kong V.; García, Idoia; Domenech, Gema; Torres, Carmen de; Alaminos Mingorance, Miguel; Ríos, José; Gerald, William L.; Kushner, Brian; LaQuaglia, Mike; Mora, Jaume
Chromosome aberrationsGene expression profilingNeoplasticNeoplasm stagingNeoplastic processesNeuroblastoma
Lavarino, C.; et al. Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma. BMC Cancer, 9:44 (2009). [http://hdl.handle.net/10481/30774]
SponsorshipThis work was supported by: Career Development Award 2001 (to J. M.) from the American Society of Clinical Oncology (ASCO). The Developmental tumour biology laboratory, Hospital Sant Joan de Déu in Barcelona, is supported by grants from the Spanish Ministry of Health (Redes Temáticas de Investigación Cooperativa 2002;G03/089), the Catalan government (AGAUR, Generalitat de Catalunya, 2005SGR00605), and the generous gift from Fondo Margarita del Pozo to the laboratory. Supported in part by the National Cancer Institute grant CA106450 (NKC and WG), The Robert Steel Foundation (NKC), Hope Street Kids (NKC), and Katie's Find A Cure Fund (NKC).
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.