Expression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations

The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate <i>KM...

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Autores principales:	Ekaterina Laukhtina, Ursula Lemberger, Andreas Bruchbacher, Dafina Ilijazi, Stephan Korn, Florian Berndl, David D’Andrea, Martin Susani, Dmitry Enikeev, Eva Compérat, Shahrokh F. Shariat, Melanie R. Hassler
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	UTUC urothelial cancer KMT2 family KMT2D histone methylation Medicine R
Acceso en línea:	https://doaj.org/article/c526ef76eb804e4084c0ace6b81a2109
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spelling	oai:doaj.org-article:c526ef76eb804e4084c0ace6b81a21092021-11-25T18:07:33ZExpression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations10.3390/jpm111111472075-4426https://doaj.org/article/c526ef76eb804e4084c0ace6b81a21092021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1147https://doaj.org/toc/2075-4426The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate <i>KMT2D</i> expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in <i>KMT2D</i> exons. Cox regression was used to assess the relationship of <i>KMT2D</i> protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, <i>p</i> = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic <i>KMT2D</i> variants and tumor location (<i>p</i> = 0.02). Pathogenic <i>KMT2D</i> variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic <i>KMT2D</i> alterations. Both IHC and NGS analyses of <i>KMT2D</i> failed to detect a statistically significant association between KMT2D protein or <i>KMT2D</i> gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all <i>p</i> > 0.05). <i>KMT2D</i> alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and <i>KMT2D</i> mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy.Ekaterina LaukhtinaUrsula LembergerAndreas BruchbacherDafina IlijaziStephan KornFlorian BerndlDavid D’AndreaMartin SusaniDmitry EnikeevEva CompératShahrokh F. ShariatMelanie R. HasslerMDPI AGarticleUTUCurothelial cancerKMT2 familyKMT2Dhistone methylationMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1147, p 1147 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	UTUC urothelial cancer KMT2 family KMT2D histone methylation Medicine R
spellingShingle	UTUC urothelial cancer KMT2 family KMT2D histone methylation Medicine R Ekaterina Laukhtina Ursula Lemberger Andreas Bruchbacher Dafina Ilijazi Stephan Korn Florian Berndl David D’Andrea Martin Susani Dmitry Enikeev Eva Compérat Shahrokh F. Shariat Melanie R. Hassler Expression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations
description	The gene coding for histone methyltransferase KMT2D is found among the top mutated genes in upper tract urothelial carcinoma (UTUC); however, there is a lack of data regarding its association with clinicopathologic features as well as survival outcomes. Therefore, we aimed to investigate <i>KMT2D</i> expression, mutation patterns, and their utility as prognostic biomarkers in patients with UTUC. A single-center study was conducted on tumor specimens from 51 patients treated with radical nephroureterectomy (RNU). Analysis of KMT2D protein expression was performed using immunohistochemistry (IHC). Customized next-generation sequencing (NGS) was used to assess alterations in <i>KMT2D</i> exons. Cox regression was used to assess the relationship of <i>KMT2D</i> protein expression and mutational status with survival outcomes. KMT2D expression was increased in patients with a previous history of bladder cancer (25% vs. 0%, <i>p</i> = 0.02). The NGS analysis of KMT2D exons in 27 UTUC tumors revealed a significant association between pathogenic <i>KMT2D</i> variants and tumor location (<i>p</i> = 0.02). Pathogenic <i>KMT2D</i> variants were predominantly found in patients with non-pelvic or multifocal tumors (60% vs. 14%), while the majority of patients with a pelvic tumor location (81% vs. 20%) did not harbor pathogenic <i>KMT2D</i> alterations. Both IHC and NGS analyses of <i>KMT2D</i> failed to detect a statistically significant association between KMT2D protein or <i>KMT2D</i> gene alteration status and clinical variables such as stage/grade of the disease or survival outcomes (all <i>p</i> > 0.05). <i>KMT2D</i> alterations and protein expression were associated with UTUC features such as multifocality, ureteral location, and previous bladder cancer. While KMT2D protein expression and <i>KMT2D</i> mutational status do not seem to have prognostic value in UTUC, they appear to add information to improve clinical decision-making regarding the type of therapy.
format	article
author	Ekaterina Laukhtina Ursula Lemberger Andreas Bruchbacher Dafina Ilijazi Stephan Korn Florian Berndl David D’Andrea Martin Susani Dmitry Enikeev Eva Compérat Shahrokh F. Shariat Melanie R. Hassler
author_facet	Ekaterina Laukhtina Ursula Lemberger Andreas Bruchbacher Dafina Ilijazi Stephan Korn Florian Berndl David D’Andrea Martin Susani Dmitry Enikeev Eva Compérat Shahrokh F. Shariat Melanie R. Hassler
author_sort	Ekaterina Laukhtina
title	Expression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations
title_short	Expression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations
title_full	Expression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations
title_fullStr	Expression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations
title_full_unstemmed	Expression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations
title_sort	expression analysis and mutational status of histone methyltransferase <i>kmt2d</i> at different upper tract urothelial carcinoma locations
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c526ef76eb804e4084c0ace6b81a2109
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Expression Analysis and Mutational Status of Histone Methyltransferase <i>KMT2D</i> at Different Upper Tract Urothelial Carcinoma Locations

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