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| Status |
Public on Apr 28, 2018 |
| Title |
Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma [Agilent] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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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| Overall design |
10 primary intrahepatic cholangiocarcinomas, 3 recurrent intrahepatic cholangiocarcinomas and 7 paracenteses from advanced disease were analyzed
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| Contributor(s) |
Peraldo-Neia C, Ostano P, Cavalloni G, Pignochino Y, Sangiolo D, De Cecco L, Marchesi E, Ribero D, Scarpa A, De Rose AM, Giuliani A, Calise F, Raggi C, Invernizzi P, Aglietta M, Chiorino G, Leone F |
| Citation(s) |
29871612 |
| Submission date |
Nov 17, 2017 |
| Last update date |
Jul 30, 2018 |
| Contact name |
Paola Ostano |
| Organization name |
Fondazione Edo ed Elvo Tempia
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| Street address |
via Malta 3
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| City |
Biella |
| ZIP/Postal code |
13900 |
| Country |
Italy |
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| Platforms (1) |
| GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE107102 |
Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma |
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| Relations |
| BioProject |
PRJNA418993 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107101_RAW.tar |
248.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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