The genetics of nephroblastoma (Wilms tumor) occurring in adults is largely unknown, as studies have largely been limited to isolated case reports. We, therefore, studied 14 adult Wilms tumors for genetic alterations, using expanded targeted sequencing on 11 cases. The patients ranged from 17 to 46 years of age (mean and median, 31 y), and there were 8 males and 6 females. Five Wilms tumors harbored BRAF V600E mutations. All of these had better-differentiated areas identical to metanephric adenoma, as has previously been described. In 3 such cases, microdissection studies revealed that the BRAF V600E mutation was present in both the metanephric adenoma and Wilms tumor areas; however, additional genetic alterations (including TERT promoter mutations in 2 cases, ASLX1/ATR mutations in 1 other case) were limited to the Wilms tumor component. These findings suggest that the Wilms tumor developed from the metanephric adenoma. Other adult Wilms tumors harbored genetic alterations previously reported in the more common pediatric Wilms tumors, including WT1 mutations (2 cases), ASLX1 mutations (3 additional cases), NSD2 mutation (1 additional case), and 11p loss (3 cases). In summary, a significant subset of adult Wilms tumors (specifically those of epithelial type with differentiated areas) harbor targetable BRAF V600E mutations and appear to arise from metanephric adenomas as a consequence of additional acquired genetic alterations. Other adult Wilms tumors often harbor genetic alterations found in their more common pediatric counterparts, suggesting at least some similarities in their pathogenesis.

成人肾母细胞瘤（肾母细胞瘤）的遗传学很大程度上未知，因为研究很大程度上仅限于孤立的病例报告。因此，我们对 11 个病例使用扩展靶向测序，研究了 14 个成人肾母细胞瘤的基因改变。患者年龄17～46岁（平均31岁），其中男性8例，女性6例。五个肾母细胞瘤携带BRAF V600E突变。正如之前所描述的，所有这些都具有与后肾腺瘤相同的更好分化的区域。在 3 个此类病例中，显微解剖研究显示BRAF V600E突变存在于后肾腺瘤和肾母细胞瘤区域；然而，其他基因改变（包括2 例中的TERT启动子突变，另外 1 例中的ASLX1/ATR突变）仅限于肾母细胞瘤成分。这些发现表明肾母细胞瘤是由后肾腺瘤发展而来。其他成人肾母细胞瘤存在先前在更常见的儿童肾母细胞瘤中报道的基因改变，包括WT1突变（2 例）、ASLX1突变（另外 3 例）、NSD2突变（另外 1 例）和 11p 缺失（3 例）。总之，成人肾母细胞瘤的一个重要子集（特别是具有分化区域的上皮型肿瘤）具有可靶向的BRAF V600E突变，并且似乎是由于额外的获得性遗传改变而由后肾腺瘤引起的。其他成人肾母细胞瘤通常含有在更常见的儿童肿瘤中发现的基因改变，这表明它们的发病机制至少有一些相似之处。