It is important to note that 1q gain and LOH at 1p/16q are not independent events. Furthermore, to the best of our knowledge, limited data have been published demonstrating the relationship between 1q gain and outcome within different tumor stages. 20- 31 Despite the strength of the data previously reported, all these studies were performed in convenience samples that were not treated consistently. The change that has been consistently reported in all such studies is a gain of chromosome 1q. Several additional studies have identified other genetic changes in FHWT that are associated with outcome. However, only 4.6% of patients with FHWT (76 of 1656 patients) had tumors with combined LOH 1p/16q, and combined LOH for 1p/16q was found to be present in only 9.4% of cases of disease recurrences (20 of 213 recurrences). 12 Furthermore, work using prospectively gathered samples as part of the NWTS-5 provided compelling data that patients with combined LOH for 1p and 16q had inferior event-free survival (EFS) and overall survival (OS), regardless of stage of disease. LOH of 1p and 16q in patients with Wilms tumor was first described from a cohort of NWTSG patients enrolled on the third and fourth National Wilms tumor studies (NWTS-3 and NWTS-4), which demonstrated inferior outcomes for patients with LOH for 16q, and trends toward inferior outcomes for patients with LOH for 1p. 19 Additional prognostic factors are necessary to prospectively identify those patients at the time of diagnosis who are at greater risk of disease recurrence. In addition, currently available therapeutic approaches expose patients to significant risk for both immediate and late morbidity and mortality, including cardiac 16 and hepatic toxicity 17 secondary malignancies 18 and pregnancy complications. 13- 15 Although the majority of patients with FHWT have good outcomes, many patients still experience disease recurrence and death from disease, even among those patients with lower disease stages. 4- 10 Multiple patient and tumor factors have been identified as being prognostically significant in the NWTSG/COG patient cohorts, including tumor histology, 2 disease stage, 11 tumor-specific loss of heterozygosity (LOH) for chromosomes 1p and 16q, 10, 12 and patient age and tumor weight. Multidisciplinary collaboration and research through the National Wilms Tumor Study Group (NWTSG), now the Renal Tumor Committee of the Children's Oncology Group (COG), as well as the European pediatric cooperative groups have led to dramatic improvements in survival for the majority of patients with FHWT. 2, 3 The absence of anaplastic features identifies patients with favorable histology Wilms tumor (FHWT), which represents the patient population analyzed in the current study. A small minority of Wilms tumors contain anaplastic histology consisting of nuclear enlargement, nuclear atypia, and irregular mitotic figures, which is associated with an increased risk of disease recurrence. 1 The majority of Wilms tumors occur in children aged < 5 years, and are characterized by a triphasic histologic pattern consisting of blastemal, stromal, and epithelial elements. Wilms tumor is the most common primary renal tumor occurring in childhood, with approximately 500 cases identified each year in the United States. A confirmatory study is necessary before this biomarker is incorporated into the risk stratification schema of future therapeutic studies. ![]() Gain of 1q may provide a valuable prognostic marker with which to stratify therapy for patients with FHWT. After stratification for stage of disease, 1q gain was associated with a significantly increased risk of disease recurrence (risk ratio estimate: 2.72 Pā=ā.0089). Gain of 1q was not found to correlate with disease stage ( Pā=ā.16). A strong relationship between 1q gain and 1p/16q loss was observed. ![]() Tumors from 58 of 212 patients (27%) displayed 1q gain. The 8-year EFS rate was 87% (95% confidence interval, 82%-91%) for the entire cohort of 212 patients. 1q gain, 1p loss, and 16q loss were determined using multiplex ligation-dependent probe amplification. Unilateral FHWT samples were obtained from patients enrolled on National Wilms Tumor Study-4 and Pediatric Oncology Group Wilms Biology Study (POG 9046). 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. ![]() Although the majority of patients with favorable histology Wilms tumor (FHWT) have good outcomes, some patients still experience disease recurrence and death from disease. Wilms tumor is the most common childhood renal tumor.
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