GNAS-mosaicism
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB56694 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR10372125_1.fastq.gz | Fastqsanger.gz | |||
| ERR10372125_2.fastq.gz | Fastqsanger.gz | |||
| ERR10387461_1.fastq.gz | Fastqsanger.gz | |||
| ERR10387461_2.fastq.gz | Fastqsanger.gz | |||
| ERR10387462_1.fastq.gz | Fastqsanger.gz |
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Project description:To investigate the effect of activating GNAS mutation on gene expression of colorectal cancer cells, we utilized the GNAS R201C knockin cell line produced by Horizon Discovery Ltd. We compared the gene expression of parental and GNAS R201C/+ HCT116 cells with RNA-Seq, using four biological replicates.
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Project description:Analysis of skin lesions from adult mice with epidermal conditional deletion of heterotrimeric G protein Galpha s in cytokeratin 14 positive cells, compared with control mouse skin. Epidermal Gnas ablation leads to skin defects, including basal cell carcinoma (BCC). Results provide insight into role of Galpha s in the regulation of stem cells from the skin. Changes in gene expression following Gnas deletion from the mouse epidermis were analyzed. Skin from four independent mice of each wild type (control) and Gnas epidermal knockout (Gnas eKO) were analyzed.
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Project description:We investigated the effect of GNAS(R201C) expression in the Kras;Gnas model of pancreatic intraductal papillary mucinous neoplasms where transgenic mutant GNAS is doxycycline inducible (LGKC; p48(Cre), Kras(LSL-G12D), Rosa26(LSL-rtTA)), Tg(TetO-GNAS(R201C)) using scRNA-seq of dissociated pancreatic tissues.
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Project description:The Gnas mutant mice driver by AdCre injection showed heterotopic osssification. In order to understand the underlying mechanism, we performed ATAC seq experiments from the control and Gnas mutant subcutaneous progenitor cells.
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Project description:The GNASR201 gain-of-function mutation is the single most frequent cancer-causing mutation across all heterotrimeric G proteins, driving oncogenesis in various low-grade/benign gastrointestinal and pancreatic tumors. In this study, we investigated the role of GNAS and its product Gαs in tumor progression using peritoneal models of colorectal cancer (CRC). GNAS was knocked out in multiple CRC cell lines harboring GNASR201C/H mutations (KM12, SNU175, SKCO1), leading to decreased cell-growth in 2D and 3D organoid models. Nude mice were peritoneally injected with GNAS-knockout KM12 cells, leading to a decrease in tumor growth and drastically improved survival at 7 weeks. Supporting these findings, GNAS overexpression in LS174T cells led to increased cell-growth in 2D and 3D organoid models, and increased tumor growth in PDX mouse models. GNAS knockout decreased levels of cyclic AMP in KM12 cells, and molecular profiling identified phosphorylation of β-catenin and activation of its targets as critical downstream effects of mutant GNAS signaling. Supporting these findings, chemical inhibition of both PKA and β-catenin reduced growth of GNAS mutant organoids. Our findings demonstrate oncogene addiction to GNAS in peritoneal models of GNASR201C/H tumors, which signal through the cAMP/PKA and Wnt/β-catenin pathways. Thus, GNAS and its downstream mediators are promising therapeutic targets for GNAS mutant tumors.
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Project description:The Gnas mutant mice driver by AdCre injection showed heterotopic osssification. In order to understand the underlying mechanism, we performed RNA seq experiments using total RNA from the control and Gnas mutant subcutaneous progenitor cells.
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