Genetic changes associated with relapse in favorable histology Wilms tumor: A Children’s Oncology Group AREN03B2 study

Finding the way to Wilms tumor by comparing the primary and relapse tumor samples

“…When investigating copy number changes, Gadd and colleagues reported a high proportion of relapses (75%) with gain of chromosome 1q, whereas this anomaly was present in 47% of paired primary tumor samples, further supporting its adverse prognostic role. 1 Similarly, yet in a smaller series of cases, we found chromosome 1q gain and/or allelic imbalance in three of eight (37.5%) primary tumor samples and in six of eight (75%) paired relapse samples. 4 Altogether these data seem to indicate that this chromosomal anomaly arises during evolution of cells in relapse or metastatic disease.…”

“…represents a relevant action in order to dissect Wilms tumor relapse. 1 We have read this paper with much interest, given that it implements a modern paradigm of research in Wilms tumor that centralizes gaining knowledge when investigating relapsing tumors, their environment, and the host, knowledge to which others and we have recently contributed. 2 , 3 , 4 …”

“…By focusing on the comparison between matched germline-primary-relapse trios, germline-relapse pairs, and relapsed Wilms tumors, Gadd and colleagues identified mutations in SIX1 gene or in genes of the MYCN network in more than 40% of relapse samples. 1 They showed that in several patients, mutations in SIX1 , MYCN (genes involved in maintaining the progenitor state in early nephrogenesis), and WTX were present in the relapse but not in the corresponding primary tumor. In particular, they found SIX1 mutations in 11 of 82 (13.4%) relapse samples, similar to our previous findings (we found four mutations in 27 analyzed relapse samples, corresponding to 14.8%).…”

“…First, the value of biological characterization of relapse is instrumental to elucidate the genomic mechanisms underlying metastasis and progression, as we and other colleagues have pointed out. 1 , 2 , 3 , 4 The availability of samples to compare between primary, relapsed Wilms tumors and the corresponding normal tissue from many patients enables us to gain insights into their spatial and temporal phylogenetic relation. Effective treatment options for many relapsing patients are still limited, and we could facilitate molecular-targeted therapies by screening relapsed tumor for actionable alterations, which could be different from primary tumor.…”

Leveraging Circulating Tumor DNA to Optimize the Initial Management of Childhood Renal Tumors

“…Disclosures provided by the author are available with this article at DOI https://doi.org/10.1200/JCO. 22…”