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Gene expression analysis of collecting duct carcinoma

ABSTRACT: Gene expression analysis of collecting duct carcinoma

PROVIDER: PRJNA644615 | ENA |

REPOSITORIES: ENA

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Gene expression analysis of collecting duct carcinoma

Project description:We performed a transcriptomic analysis in a cohort of 6 Collecting Duct Carcinoma, 5 Clear Cell Renal Cell Carcinoma and 4 non-matched normal renal tissues to unravel the underlying biological and molecular determinants and to identifiy specific genes and pathways of this rare tumor type.

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Gene expression of collecting duct carcinoma of the kidney

Project description:The genetic landscape and molecular features of collecting duct carcinoma (CDC) of the kidney remain largely unknown. Herein, we performed whole exome sequencing (WES) and transcriptome sequencing (RNASeq) on 7 CDC samples (CDC1 -7). Among the 7 samples, 4 samples with matched non-tumor tissue were used for copy number analysis by SNP array data. No recurrent somatic SNVs were observed except for MLL, which was found to be mutated (p.V297I and p.F407C) in 2 samples. We identified somatic SNVs in 14 other cancer census genes including: ATM, CREBBP, PRDM1, CBFB, FBXW7, IKZF1, KDR, KRAS, NACA, NF2, NUP98, SS18, TP53, and ZNF521. SNP array data identified a CDKN2A homozygous deletion in 3 samples and SNV analysis showed a non-sense mutation of the CDKN2A gene with unknown somatic status. To estimate the recurrent rate of CDKN2A abnormalities, we performed FISH screening of additional samples and confirmed the frequent loss (62.5%) of CDKN2A expression. Since cisplatin based therapy is the common treatment option for CDC, we investigated the expression of solute carrier (SLC) family transporters and found 45% alteration. In addition, SLC7A11 (cystine transporter, xCT), a cisplatin resistance associated gene, was found to be overexpressed in 4 out of 5 (80%) cases of CDC tumors tested, as compared to matched non-tumor tissue. In summary, our study provides a comprehensive genomic analysis of CDC and identifies potential pathways suitable for targeted therapies.

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Human iPSC-derived renal collecting duct organoids model cystogenesis in ADPKD

Project description:Here, establishing expansion cultures of hiPSC-derived ureteric bud tip cells, an embryonic precursor that gives rise to collecting ducts, we succeeded in advancing the developmental stage of collecting duct organoids and showed that all collecting duct organoids derived from PKD1-/- hiPSCs spontaneously develop multiple cysts, clarifying the initiation mechanisms of cystogenesis.

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