KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas
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RESEARCH ARTICLE
Open Access
KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas Aida Catic1,2* , Amina Kurtovic-Kozaric2,3, Ardis Sophian1, Lech Mazur1, Faruk Skenderi3, Ondrej Hes4, Stephen Rohan5, Dinesh Rakheja6,7, Jillene Kogan1,8,9,10 and Michael R. Pins8,9
Abstract Background: Metanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell carcinoma in adults and Wilms̕ tumor in children. Despite recent advancements in tumor genomics, there is limited data available regarding the genetic alterations characteristic of MA. The purpose of this study is to determine the frequency of metanephric adenoma cases exhibiting cytogenetic aberration t (9;15)(p24;q24), and to investigate the association between t (9,15) and BRAF mutation in metanephric adenoma. Methods: This study was conducted on 28 archival formalin fixed paraffin-embedded (FFPE) specimens from patients with pathologically confirmed MA. Tissue blocks were selected for BRAF sequencing and fluorescent in situ hybridization (FISH) analysis for chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3), which was previously characterized and described in two MA cases. Results: BRAFV600E mutation was identified in 62% of our cases, 9 (38%) cases were BRAFWT, and 4 cases were uninformative. Of the 20 tumors with FISH results, two (10%) were positive for KANK1-NTRK3 fusion. Both cases were BRAFWT suggesting mutual exclusivity of BRAFV600E and KANK1-NTRK3 fusion, the first such observation in the literature. Conclusions: Our data shows that BRAF mutation in MA may not be as frequent as suggested in the literature and KANK-NTRK3 fusions may account for a subset of BRAFWT cases in younger patients. FISH analysis for KANK1-NTRK3 fusion or conventional cytogenetic analysis may be warranted to establish the diagnosis of MA in morphologically and immunohistochemically ambiguous MA cases lacking BRAF mutations. Keywords: Metanephric adenoma, Cytogenetics, Chromosomal translocations, KANK1-NTRK3 fusion, BRAFV600E
Background Metanephric adenoma (MA) is a rare benign renal tumor classified under the rubric of metanephric tumors, which also include metanephric stromal tumor and metanephric adenofibroma [1]. BRAF mutations * Correspondence: [email protected] 1 Department of Cytogenetics, ACL Laboratories, Rosemont, IL, USA 2 Department of Genetics and Bioengineering, International Burch University, Francuske revolucije bb, Ilidza, 71000 Sarajevo, Bosnia and Herzegovina Full list of author information is available at the end of the article
have been identified in metanephric stromal tumor and metanephric adenofibroma in addition to metanephric adenoma, which justifies their grouping as family of metanephric tumors by the World Health Organization (WHO) [2]. MA is uncommon and generally occurs in adults between the fourth and sixth decades of life and occasionally in children [3]. The male
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