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Cytogenetic abnormalities and clinical outcome in Wilms tumor: A study by the UK Cancer Cytogenetics Group and the UK Children's Cancer Study Group

Lookup NU author(s): Dr Nicholas Bown, Simon Cotterill, Dr Michael Griffiths

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Abstract

Background. Tumor genetic features reported to correlate with adverse outcome in Wilms tumor include karyotype complexity, losses of material from the short arm of chromosome 1 and from the long arms of chromosomes 11, 16 and 22 and gain of Material from the long arm of chromosome 1. This study sought to test these associations in a large series of tumors studied by cytogenetic analysis. Identification of markers associated with elevated risk of relapse and fatal outcome could allow more effective treatment stratification at presentation, Procedure, Thirteen member laboratories of the U.K. Cancer Cytogenetics Group provided results from a 12-year period. Karyotype abnormalities were correlated with clinical data (age, tumor stage, and histology) and outcome data provided by the central register of the U.K. Children's Cancer Study Group. Results. Of 127 abnormal karyotypes, 78 included a reputedly "poor prognosis" feature. Univariate survival analysis showed no significant adverse effect for karyotype complexity, 1 p loss or 11 q loss. The poor outcome of cases with 16q loss was of borderline significance, but this effect was restricted to those tumors with unbalanced translocation der(16)t(1q;16q). The association between relapse risk and gain of 1q material was not significant. Only monosomy 22 was a significant marker of poor outcome in univariate analysis (13 cases showing 50% relapse free survival at 5 years compared to 79% survival for the remaining 114 cases, P=0.02), In multivariate analysis, significant independent predictors of poor outcome were 1q gain (Hazard Ratio 3.4), stage IV disease (HR 5.0), and monosomy 22 (HR 5.9). Conclusions. Loss of chromosome 22 identifies high risk Wilms tumors. The prognostic significance of 1q gain, 16q loss and unbalanced translocation der(16)t(1q;16q) is unresolved and warrants further investigation. (C) 2002 Wiley-Liss, Inc.


Publication metadata

Author(s): Bown N; Cotterill SJ; Griffiths M; Roberts P; Larkins S; Hibbert S; Middleton H; Kelsey A; Tritton D; Mitchell C

Publication type: Article

Publication status: Published

Journal: Medical and Pediatric Oncology

Year: 2002

Volume: 38

Issue: 1

Pages: 11-21

ISSN (print): 0098-1532

ISSN (electronic): 1096-911X

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/mpo.1258

DOI: 10.1002/mpo.1258


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