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Genetic changes of sotorasib-resistant cells

ABSTRACT: Genetic changes of sotorasib-resistant cells

PROVIDER: PRJEB55843 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR10162504_1.fastq.gz	Fastqsanger.gz
	ERR10162504_2.fastq.gz	Fastqsanger.gz
	ERR10162505_1.fastq.gz	Fastqsanger.gz
	ERR10162505_2.fastq.gz	Fastqsanger.gz
	ERR10162506_1.fastq.gz	Fastqsanger.gz

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Genetic changes of sotorasib-resistant cells

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Project description:To characterize sotorasib resistance in lung adenocarcinomas (LUAD), we generated genetically engineered mice (Kras-G12C, Trp53-KO) and compared the transcriptional profiles of untreated and sotorasib-resistant tumors

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Project description:NCI-H358 is a KRAS G12C-mutant non-small lung cancer cell line known to be sensitive to KRAS G12C-inhibitor sotorasib. Here, we aimed to develop sotorasib resistance in H358 and interrogate the resulting sotorasib-resistant cell line (H358-R). The H358-R cell line was created by continuous culturing of the H358 cells in sotorasib (250 nM) until cells grew readily under sotorasib pressure (approximately 2 months). We then performed RNA-seq of the resulting sotorasib-resistant cell line (H358-R) with and without sotorasib pressure, compared to the parental sensitive cell line control (H358). KRAS gene expression level was found to be increased in the sotorasib-resistant line compared with the parental cells, likely representing a mechanism of resistance. The increased KRAS expression level in the resistant cell line was maintained under sotorasib pressure.

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