Cargando…

KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas

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 availabl...

Descripción completa

Detalles Bibliográficos
Autores principales: Catic, Aida, Kurtovic-Kozaric, Amina, Sophian, Ardis, Mazur, Lech, Skenderi, Faruk, Hes, Ondrej, Rohan, Stephen, Rakheja, Dinesh, Kogan, Jillene, Pins, Michael R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552490/
https://www.ncbi.nlm.nih.gov/pubmed/33046021
http://dx.doi.org/10.1186/s12881-020-01143-6
_version_ 1783593411073277952
author Catic, Aida
Kurtovic-Kozaric, Amina
Sophian, Ardis
Mazur, Lech
Skenderi, Faruk
Hes, Ondrej
Rohan, Stephen
Rakheja, Dinesh
Kogan, Jillene
Pins, Michael R.
author_facet Catic, Aida
Kurtovic-Kozaric, Amina
Sophian, Ardis
Mazur, Lech
Skenderi, Faruk
Hes, Ondrej
Rohan, Stephen
Rakheja, Dinesh
Kogan, Jillene
Pins, Michael R.
author_sort Catic, Aida
collection PubMed
description 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: BRAF(V600E) mutation was identified in 62% of our cases, 9 (38%) cases were BRAF(WT), and 4 cases were uninformative. Of the 20 tumors with FISH results, two (10%) were positive for KANK1-NTRK3 fusion. Both cases were BRAF(WT) suggesting mutual exclusivity of BRAF(V600E) 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 BRAF(WT) 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.
format Online
Article
Text
id pubmed-7552490
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-75524902020-10-13 KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas Catic, Aida Kurtovic-Kozaric, Amina Sophian, Ardis Mazur, Lech Skenderi, Faruk Hes, Ondrej Rohan, Stephen Rakheja, Dinesh Kogan, Jillene Pins, Michael R. BMC Med Genet Research Article 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: BRAF(V600E) mutation was identified in 62% of our cases, 9 (38%) cases were BRAF(WT), and 4 cases were uninformative. Of the 20 tumors with FISH results, two (10%) were positive for KANK1-NTRK3 fusion. Both cases were BRAF(WT) suggesting mutual exclusivity of BRAF(V600E) 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 BRAF(WT) 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. BioMed Central 2020-10-12 /pmc/articles/PMC7552490/ /pubmed/33046021 http://dx.doi.org/10.1186/s12881-020-01143-6 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Catic, Aida
Kurtovic-Kozaric, Amina
Sophian, Ardis
Mazur, Lech
Skenderi, Faruk
Hes, Ondrej
Rohan, Stephen
Rakheja, Dinesh
Kogan, Jillene
Pins, Michael R.
KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas
title KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas
title_full KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas
title_fullStr KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas
title_full_unstemmed KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas
title_short KANK1-NTRK3 fusions define a subset of BRAF mutation negative renal metanephric adenomas
title_sort kank1-ntrk3 fusions define a subset of braf mutation negative renal metanephric adenomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552490/
https://www.ncbi.nlm.nih.gov/pubmed/33046021
http://dx.doi.org/10.1186/s12881-020-01143-6
work_keys_str_mv AT caticaida kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT kurtovickozaricamina kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT sophianardis kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT mazurlech kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT skenderifaruk kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT hesondrej kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT rohanstephen kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT rakhejadinesh kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT koganjillene kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas
AT pinsmichaelr kank1ntrk3fusionsdefineasubsetofbrafmutationnegativerenalmetanephricadenomas