Concurrent Reduced Expression of Contiguous PKD1, TSC2 and NTHL1 Leading to Kidney Diseases and Multiple Diverse Renal Cancers.

Autor:	Meguro S; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan s-meguro@fmu.ac.jp., Koguchi T; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Hakozaki Y; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Onagi A; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Matsuoka K; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Hoshi S; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Hata J; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Sato Y; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Akaihata H; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Kataoka M; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Ogawa S; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan., Kojima Y; Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Jazyk:	angličtina
Zdroj:	Cancer genomics & proteomics [Cancer Genomics Proteomics] 2023 Jan-Feb; Vol. 20 (1), pp. 40-50.
DOI:	10.21873/cgp.20363
Abstrakt:	Background/aim: Several cases of concurrent reduction of expression of polycystin 1 (PKD1) and Tuberous Sclerosis Complex 2 (TSC2) that are contiguous in chromosome 16p13 have been previously reported. This study newly addresses the concurrent reduction of expression of PKD1, TSC2 and NTHL1, which is adjacent to TSC2 and is a tumor suppressor gene. Materials and Methods: We investigated the mRNA expression levels of PKD1, TSC2, PKD2, TSC1 and NTHL1 in blood and renal cell carcinoma (RCC) tissues in a proband with autosomal dominant polycystic kidney disease (ADPKD), tuberous sclerosis complex (TSC) and multiple pathologically diverse RCCs, including clear cell, papillary and chromophobe types. Additionally, we investigated germline variants in blood using whole exome sequencing (WES) in the proband and her four siblings. Results: mRNA expression levels of PKD1, TSC2 and NTHL1 were reduced in the proband's blood and RCCs, compared with control groups. WES identified one novel variant with amino acid changes in the PKD1 exon in the three subjects with ADPKD, including the proband. Moreover, two variants in the TSC2 intron specific to the proband were also identified. Conclusion: In this study, we report a novel pathogenic variant in the PKD1 exon which likely led to ADPKD, and two variants in the TSC2 intron, which might have led to reduction in the expression of both TSC2 and NTHL1, consequently leading to TSC and multiple pathologically diverse RCCs. (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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