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- Title
Specific gene expression profiles and chromosomal abnormalities are associated with infant disseminated neuroblastoma.
- Authors
Lavarino, Cinzia; Cheung, Nai-Kong V.; Garcia, Idoia; Domenech, Gema; de Torres, Carmen; Alaminos, Miguel; Rios, Jose; Gerald, William L.; Kushner, Brian; LaQuaglia, Mike; Mora, Jaume
- 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.
- Subjects
NEUROBLASTOMA; CHROMOSOME abnormalities; NERVOUS system tumors; SPONTANEOUS cancer regression; DISEASE remission; CANCER in infants; GENE expression
- Publication
BMC Cancer, 2009, Vol 9, p1
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/1471-2407-9-44