Loss of Heterozygosity for Chromosomes 1p and 16q Is an Adverse Prognostic Factor in Favorable-Histology Wilms Tumor: A Report From the National Wilms Tumor Study Group

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Abstract
Purpose To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). Patients and Methods Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. Results LOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). Conclusion Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.