Gain of 1q is associated with inferior event-free and overall survival in patients with favorable histology Wilms tumor: a report from the Children's Oncology Group - PubMed (original) (raw)

Multicenter Study

. 2013 Nov 1;119(21):3887-94.

doi: 10.1002/cncr.28239. Epub 2013 Aug 26.

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Multicenter Study

Gain of 1q is associated with inferior event-free and overall survival in patients with favorable histology Wilms tumor: a report from the Children's Oncology Group

Eric J Gratias et al. Cancer. 2013.

Abstract

Background: Wilms tumor is the most common childhood renal tumor. Although the majority of patients with favorable histology Wilms tumor (FHWT) have good outcomes, some patients still experience disease recurrence and death from disease. The goal of the current study was to determine whether tumor-specific chromosome 1q gain is associated with event-free survival (EFS) and overall survival (OS) in patients with FHWT.

Methods: Unilateral FHWT samples were obtained from patients enrolled on National Wilms Tumor Study-4 and Pediatric Oncology Group Wilms Biology Study (POG 9046). 1q gain, 1p loss, and 16q loss were determined using multiplex ligation-dependent probe amplification.

Results: The 8-year EFS rate was 87% (95% confidence interval [95% CI], 82%-91%) for the entire cohort of 212 patients. Tumors from 58 of 212 patients (27%) displayed 1q gain. A strong relationship between 1q gain and 1p/16q loss was observed. The 8-year EFS rate was 76% (95% CI, 63%-85%) for patients with 1q gain and 93% (95% CI, 87%-96%) for those lacking 1q gain (P = .0024). The 8-year OS rate was 89% (95% CI, 78%-95%) for those with 1q gain and 98% (95% CI, 94%-99%) for those lacking 1q gain (P = .0075). Gain of 1q was not found to correlate with disease stage (P = .16). After stratification for stage of disease, 1q gain was associated with a significantly increased risk of disease recurrence (risk ratio estimate: 2.72; P = .0089).

Conclusions: Gain of 1q may provide a valuable prognostic marker with which to stratify therapy for patients with FHWT. A confirmatory study is necessary before this biomarker is incorporated into the risk stratification schema of future therapeutic studies.

Keywords: Wilms tumor; chromosome 1; kidney; pediatrics; prognosis.

© 2013 American Cancer Society.

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Figures

Figure 1

Figure 1

Event-free survival stratified for 1q gain

Figure 2

Figure 2

Overall survival stratified for 1q gain

Figure 3

Figure 3

Mechanisms responsible for 1q gain A. Translocations involving chromosome 1 (the most common also involves chromosome 16). All tumors with t(1;16) examined thus far show loss of the der(1) and retention of the der(16). This results in loss of copy number and LOH for 1p and 16q. Tumors also variably show duplication of the normal chromosomes 1 and/or 16. While this increases the copy number for these chromosomal arms, because there are two exact copies, LOH is seen. B. Isochromosome 1q results from the development of a derivative chromosome 1 that contains two mirror-image copies of 1q. The normal chromosome 1 remains, resulting in 1q gain and 1p LOH. Again, the normal chromosome 1 is often duplicated, resulting in copy neutral LOH for 1p.

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