1. Allele loss at 16q defines poorer prognosis Wilms tumour irrespective of treatment approach in the UKW1-3 clinical trials: a Children's Cancer and Leukaemia Group (CCLG) Study.
- Author
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Messahel B, Williams R, Ridolfi A, A'hern R, Warren W, Tinworth L, Hobson R, Al-Saadi R, Whyman G, Brundler MA, Kelsey A, Sebire N, Jones C, Vujanic G, and Pritchard-Jones K
- Subjects
- Chemotherapy, Adjuvant, Child, Preschool, Chromosomes, Human, Pair 1 genetics, Humans, Infant, Infant, Newborn, Kidney Neoplasms pathology, Kidney Neoplasms therapy, Microsatellite Repeats genetics, Neoadjuvant Therapy, Neoplasm Staging, Nephrectomy, Polymerase Chain Reaction methods, Prognosis, Survival Analysis, Treatment Outcome, Wilms Tumor pathology, Wilms Tumor therapy, Chromosomes, Human, Pair 16 genetics, Kidney Neoplasms genetics, Loss of Heterozygosity, Wilms Tumor genetics
- Abstract
Survival from Wilms tumour is excellent. Hence, better markers are required to restrict treatments causing late sequelae to those at highest risk of relapse. We investigated the prognostic significance of loss of heterozygosity (LOH) on 1p and 16q in 426 favourable histology Wilms tumours treated with either immediate nephrectomy (63%) or preoperative chemotherapy (37%). Four years RFS and OS were 84.6% and 92.0%, respectively. 10.3% tumours had LOH 1p, 14.6% LOH 16q, with 2.6% at both loci. In multivariate analysis, LOH 16q was associated with an increased risk of relapse (hazard ratio (HR) 2.69, 95%CI: 1.47-4.92) and death (HR 2.67, 95%CI: 1.17-6.06). LOH 1p showed no significant associations. These results were not influenced by treatment approach. LOH 16q is an adverse risk factor in favourable histology Wilms tumour, regardless of initial approach to therapy. Its relationship with histological risk groups defined after neo-adjuvant chemotherapy requires analysis in a larger series, and is the subject of the current SIOP WT 2001 trial.
- Published
- 2009
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