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Molecular cytogenetic definition of 17q translocation breakpoints in neuroblastoma

Lookup NU author(s): Dr Maria Lastowska, Dr Nicholas Bown, Professor John LunecORCiD, Professor Tom Strachan, Professor Andrew Pearson, Dr Michael Jackson


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Background. It is now recognized that gain of chromosome 17 material is the most frequent genetic abnormality of neuroblastoma cells. Several studies have linked 17q gain with known adverse prognostic factors: Patient age >1 year, advanced stage disease, deletion of chromosome arm 1 p, and amplification of the MYCN oncogene. We sought to further investigate the clinical and prognostic associations of chromosome 17 status in relation to other well-established predictive factors. Procedure. In a collaborative study by UK cytogenetics centres, we compiled a series of 104 neuroblastoma tumours for which the status of chromosome 17 was confidently defined by cytogenetics, metaphase or interphase FISH, or CGH analysis. The results were correlated with data on 1 p and MYCN, and with centrally collated clinical and survival information. Results. Gain of 17q (i.e., unbalanced gain of segment 17q21-qter) was found in 66.3% of tumours, while 33.7% showed a '17q normal' status (i.e., no gain at all, or gain of whole chromosome 17 relative to ploidy). Gain of 17q was strongly associated with advanced stage disease, patient age >1 year, 1p deletion, and MYCN amplification (all P < 0.01). In univariate analysis, 17q gain was a significant predictor of adverse outcome (projected 5 year relapse-free survival 15.6% compared to 75.2% in cases lacking this feature in tumour cells; (P < 0.0001). In multivariate analysis, 17q gain was more strongly associated with adverse outcome than was either stage (Stage 4 vs other combined) or 1p status. Conclusion. We conclude that gain of chromosome segment 17q21-qter is of great biological and clinical importance in neuroblastoma, and that its detection at diagnosis should be a priority. © 2001 Wiley-Liss, Inc.

Publication metadata

Author(s): Lastowska M, van Roy N, Bown NP, Speleman F, Roberts P, Lunec J, Strachan T, Pearson ADJ, Jackson MS

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: 8th Advances in Neuroblastoma Research Conference (1998)

Year of Conference: 2001

Pages: 20-23

ISSN: 1545-5009

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/1096-911X(20010101)36:1<20::AID-MPO1006>3.0.CO;2-E

Series Title: Medical and Pediatric Oncology