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: | , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/c526ef76eb804e4084c0ace6b81a2109 |
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| Sumario: | 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. |
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