BRAF mutations in pediatric metanephric tumors

Abstract

Metanephric neoplasms of the kidney are uncommon, and some cases are associated with papillary carcinoma. Most cases of metanephric adenoma occur in adults, with fewer than 25 cases reported in children, and metanephric adenofibroma is even less common. The few metanephric tumors studied at the genetic level have not shown the gains of chromosomes 7 and 17 commonly seen in renal cell carcinoma, suggesting that the carcinoma arising in this setting has a separate genetic origin from the adenoma. However, the assumption that this carcinoma has the same chromosome gains as sporadic renal cell carcinoma has never been validated. We studied 4 cases of metanephric tumors in children, including 1 metanephric adenofibroma with papillary carcinoma. The composite tumor was studied by single nucleotide polymorphism array and fluorescence in situ hybridization, with the adenoma and carcinoma components analyzed separately. No copy number alterations were detected in either component. A BRAF V600E mutation has been reported in most cases of metanephric adenoma in adults. We performed BRAF V600E immunostaining and sequencing in our 4 pediatric cases. Three cases had a BRAF V600E mutation including the composite tumor, with both the adenoma and carcinoma components showing the same mutation. This finding provides the first genetic evidence that these 2 tumors are biologically linked. Ten cases each of pediatric renal cell carcinoma and Wilms tumor were immunonegative. Thus, BRAF V600E immunostaining is a helpful marker for pediatric metanephric adenoma, and additional research is required on the possible role of this mutation in the development of renal carcinoma.

Keywords: BRAF V600E mutation; FISH; Metanephric adenofibroma; Metanephric adenoma; Papillary carcinoma; SNP array.