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Breakpoint position on 17q identifies the most aggressive neuroblastoma tumors

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


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Gain of chromosome arm 17q is a powerful prognostic factor in neuroblastoma, and the distribution of 17q breakpoints suggests that the dosage of one or more genes in 17q22-23 to 17qter is critical for tumor progression. To identify the smallest region of 17q gain, we used eight probes to map translocation breakpoints in 48 primary neuroblastoma tumors. We identified at least five different breakpoints, all localized within the proximal part of 17q (from D17Z1 to MPO). The shortest region of gain identified by these probes extends from MPO (17q23.1) to 17qter. Surprisingly, we found that breakpoints localized proximal to ERBB2 (17q 12) were associated with significantly better patient survival than breakpoints localized distal to ERBB2. Breakpoints localized distal to ERBB2 identified patients with a particularly poor prognosis, higher mitotic karyorrhectic index, and stage 4 disease. This implies that breakpoint position on 17q is a discriminative factor within this prognostically poor group of patients. This result also suggests that the biological effect of 17q gain during neuroblastoma progression has a complex basis. We propose that this involves dosage alterations of genes localized on both sides of the 17q breakpoints, with a gene or genes mapping between 17cen and 17q 12 acting to suppress progression, and a gene or genes mapping between 17q23.1 and 17qter acting to promote tumor progression. © 2002 Wiley-Liss, Inc.

Publication metadata

Author(s): Lastowska, M., Cotterill, C., Bown, N., Cullinane, C., Variend, S., Lunec, J., Strachan, T., Pearson, A.D.J., Jackson, M.S.

Publication type: Article

Publication status: Published

Journal: Genes Chromosomes and Cancer

Year: 2002

Volume: 34

Issue: 4

Pages: 428-436

Print publication date: 01/01/2002

ISSN (print): 1045-2257

ISSN (electronic): 1098-2264


DOI: 10.1002/gcc.10089

PubMed id: 12112532


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