Genetic Changes Associated With Relapse in Favorable Histology Wilms Tumor - A Children’s Oncology Group AREN03B2 Study

Cell Reports Medicine. Volume 3, Issue 6, 100644, 21 June 2022 10.1016/j.xcrm.2022.100644

In the last decade, sequencing of primary tumors has clarified the genetic underpinnings of Wilms tumor, yet has not impacted therapy, outcome, or toxicities. We now sharpen our focus on relapse samples from the umbrella AREN03B2 study. We show that over 40% of relapse samples contain mutations in SIX1 or genes of the MYCN network, drivers of progenitor proliferation. Not previously seen in large studies of primary Wilms tumors, DIS3 and TERT are now identified as recurrently mutated. The analysis of primary-relapse tumor pairs suggests that 11p15 loss of heterozygosity (and other copy number changes) and mutations in WT1, MLLT1 typically occur early, however mutations in SIX1, MYCN, and WTX are late developments in some patients. Most strikingly, 75% of relapse samples had gain of 1q, providing strong conceptual support for studying circulating tumor DNA in clinical trials in order to better detect 1q gain earlier and to monitor response.

Data in the GDC

• GDC Manifests
• MP2PRT-WT RNA-Seq HTSeq Transcript Counts (GENCODE v22) - Download Manifest (63 files)
• MP2PRT-WT WGS BRASS Structural Variation (GENCODE v22) - Download Manifest (98 files)
• MP2PRT-WT WGS ASCAT Gene Level Copy Number Variation (GENCODE v22) - Download Manifest (98 files)
• MP2PRT-WT WGS ASCAT Genomic Copy Number Variation - Download Manifest (98 files)
• MP2PRT-WT WGS CaVEMan Somatic Mutation VCFs - Download Manifest (98 files)
• MP2PRT-WT WGS Pindel Somatic Mutation VCFs - Download Manifest (98 files)

Supplemental Data

• Associated Data Files
• Supplemental Table 1.xlsx - Supplementary Table 1: Filtered SNV calls
• Supplemental Table 2.xlsx - Supplementary Table 2: Filtered structural and germline variants
• Supplemental Table 3.xlsx - Supplementary Table 3: Selected copy number data
• Supplemental Table 4.xlsx - Supplementary Table 4: Validation variants
• Supplemental Figure1_03102022.pdf - Supplemental Figure 1

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