Embryonal precursors of Wilms tumor

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Science  06 Dec 2019:
Vol. 366, Issue 6470, pp. 1247-1251
DOI: 10.1126/science.aax1323

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A childhood tumor—from the beginning

Many adult cancers arise from clonal expansions of mutant cells in normal tissue. These premalignant expansions are defined by somatic mutations shared by the cancers. Whether pediatric cancers originate in a similar way is unknown. Coorens et al. studied Wilms tumor, a childhood kidney cancer. Phylogenetic analyses revealed large clones of mutant cells in histologically and functionally normal kidney tissue long before tumor development. Thus, like adult tumors, Wilms tumor appears to arise from a premalignant tissue bed.

Science, this issue p. 1247


Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the H19 locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.

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