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Adult Wilms Tumor: Genetic Evidence of Origin of a Subset of Cases From Metanephric Adenoma.

ABSTRACT: 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.

SUBMITTER: Argani P

PROVIDER: S-EPMC9310085 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Adult Wilms Tumor: Genetic Evidence of Origin of a Subset of Cases From Metanephric Adenoma.

Argani Pedram P Tickoo Satish K SK Matoso Andres A Pratilas Christine A CA Mehra Rohit R Tretiakova Maria M Sibony Mathilde M Meeker Alan K AK Lin Ming-Tseh MT Reuter Victor E VE Epstein Jonathan I JI Gagan Jeffrey J Palsgrove Doreen N DN

The American journal of surgical pathology 20220221 7

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 adeno ...[more]

PMID: 35184066

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Project description:Metanephric adenoma (MA) of the kidney is a rare, indolent tumor that may be difficult to differentiate from other small renal masses (SRMs). Genetic alterations associated with MA remain largely unknown.We aimed at defining genetic events in MA of the kidney and determining their influence in the management of this disease.Multiplexed mass spectrometric genotyping was performed on 29 MA cases after tumor DNA extraction. We also conducted a mutational screen in an additional 129 renal neoplasms. Immunohistochemistry was performed on the MA cases to assess molecular markers of signaling pathway activation. Patients' baseline characteristics, as well as follow-up data, were captured.We used descriptive statistics for baseline clinical characteristics and incidence of mutations. The Wilcoxon rank-sum test was used to correlate patient characteristics with mutational status.We identified the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation in 26 of 29 MA cases. These results were validated in all cases using the commercially available BRAF Pyro Kit (QIAGEN). In contrast, BRAF mutations were rare in the other 129 non-MA renal neoplasms that were screened. We detected a BRAF mutation (V600E) in only one papillary renal cell carcinoma case. In all MA tumors, we documented expression of phosphorylated mitogen-activated protein kinase and phosphorylated extracellular signal-regulated kinase, accompanied by immunoreactivity for p16 (INK4a). All patients were treated with a partial or radical nephrectomy, and after a median follow-up of 26.5 mo, there were no local or distant recurrences. Limitations include the retrospective nature of this study.BRAF V600E mutations are present in approximately 90% of all MA cases, serving as a potential valuable diagnostic tool in the differential diagnosis of SRMs undergoing a percutaneous biopsy. The presence of BRAF V600E and mitogen-activated protein kinase activation in a largely benign tumor supports the necessity for secondary events (e.g., p16 loss) in BRAF-driven oncogenesis.

Dataset Information

Adult Wilms Tumor: Genetic Evidence of Origin of a Subset of Cases From Metanephric Adenoma.

Publications

Adult Wilms Tumor: Genetic Evidence of Origin of a Subset of Cases From Metanephric Adenoma.

Similar Datasets

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