The frequency of a novel KANK1 and NTRK3 translocation and BRAFV600E mutation in patients diagnosed with metanephric adenoma utilizing molecular mechanisms.

Abstract

1537 Background: Renal metanephric adenoma (MA) is a very rare benign renal tumor, which is frequently misclassified when microscopic features alone are applied. Despite the classification of adenoma as a benign tumor, it is difficult to differentiate from other renal carcinomas such as malignant papillary renal cell carcinomas and in children it can be mistaken with Wilms tumor. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, there is limited data available regarding the genetic alterations critical to the metanephric adenoma development. Recent data suggest that 90% of MA have BRAFV600Emutations; the genetics of the remaining 10 % are unclear. Methods: This study was conducted on 13 FFPE specimens from patients who were diagnosed with renal metanephric adenoma. H&E stained slides from all cases were reviewed by study pathologist, and representative tissue blocks were further selected for BRAFV600E sequencing and fluorescent in situ hybridization was adapted to detect chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3). Results: In this study, we identified a novel chromosomal translocation t(9;15)(p24;q24) between KANK1 and NTRK3, and provided new insights into molecular mechanisms which might identify a subset of metanephric adenomas. Such findings imply that recurrent cytogenetic aberrations may be of prognostic significance as well. Interestingly, our data suggested mutual exclusivity of BRAFV600Eand t(9;15) aberrations. Conclusions: Molecular and cytogenetic analyses have allowed us to elucidate a genetic aberration, which may be specific to metanephric adenoma. Aberrant expression of the KANK1-NTRK3 gene fusion may be one mechanism by which functionally relevant genes are altered in the development of metanephric adenoma, and thus mark a subgroup of metanephric adenomas with particular clinicopathological features. Also, our study adds KANK1 and NTRK3 to the list of candidate genes that may play a role in the 10% of renal metanephric adenomas that lack a BRAFV600E mutation.