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Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107102 | GEO | 2018/04/28

REPOSITORIES: GEO

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Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma.

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Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma [Agilent]

Project description:Purpose: Effective target therapies for intrahepatic cholangiocarcinoma have not been identified so far. One of the reasons may be the molecular and genomic alteration difference between paired primary (PR) and recurrent (REC) tumors. We aim to identify peculiar characteristics and to select potential targets specific for recurrent tumors. Experimental design: Thirteen ICC pairs from Italian patients were collected and analyzed for gene expression profiling and mutational status of IDH1. For two pairs, deep mutational analysis by Next Generation Sequencing was also carried out. An independent cohort of patients was used for validation. Results: Two class paired comparison yielded 315 differentially expressed genes between REC and PR tumors. Up-regulated genes in RECs are involved in RNA/DNA processing, cell cycle, epithelial to mesenchymal transition (EMT), resistance to apoptosis, and cytoskeleton remodeling. Down-regulated genes participate to epithelial cell differentiation, proteolysis, apoptotic, immune response, and inflammatory processes. A 24 gene signature is able to discriminate RECs from PRs, and 9 genes predict recurrence in an independent cohort; FANCG is statistically associated with survival in the chol-TCGA dataset. IDH1 was mutated in the RECs of three patients. In the independent cohort, 2 out of 5 patients displayed the IDH1 mutation only in RECs. Deep sequencing revealed TP53, ASXL1, PTEN and DICER1 novel mutations. Conclusions: RECs displayed more aggressive phenotype; EMT, resistance to apoptosis, and cytoskeleton remodeling were key players and druggable pathways in REC. IDH1 is mutated in about 30% of patients, becoming a marker of progression and a target for therapy.

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Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma

Project description:Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma

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