Summary of Study ST002835
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001775. The data can be accessed directly via it's Project DOI: http://dx.doi.org/10.21228/M88M6V This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002835 |
| Study Title | Investigation of FGFR signaling controlled metabolism in FGFR2-fusion+ intrahepatic cholangiocarcinoma |
| Study Summary | Genomic alterations that activate FGFR2 are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to treatment with FGFR inhibitors. However, the depth and duration of responses are often limited. Elucidating the FGFR2-driven oncogenic program and the adaptions to FGFR inhibition is needed to gain insight into the biology of these tumors and inform future therapeutic development. Here, we conducted metabolomic analysis of patient-derived models to define the pathways that fuel tumor growth downstream of oncogenic FGFR2 signaling in ICC and to uncover compensatory mechanisms associated with pathway inhibition. We find FGFR2-fusion+ ICC maintains a highly glycolytic phenotype in FGFR2+ ICC. Conversely, FGFR inhibition blocks glucose uptake and glycolysis, while inciting a series of adaptive changes. Thus, we show that glycolysis is a key downstream effector of oncogenic FGFR2 signaling in ICC, and that pronounced metabolic reprogramming in response to FGFR inhibition confers new targetable vulnerabilities. |
| Institute | Massachusetts General Hospital |
| Last Name | Zhen |
| First Name | Yuanli |
| Address | 185 cambridge street, room 4100 |
| yzhen1@mgh.harvard.edu | |
| Phone | 4698792279 |
| Submit Date | 2023-08-26 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-03-20 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004631 | AN004632 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Thermo Vanquish | Thermo Vanquish |
| Column | Thermo BETASIL Diol (150 x 2.1mm,5um) | Thermo BETASIL Diol (150 x 2.1mm,5um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Orbitrap ID-X tribrid | Thermo Orbitrap ID-X tribrid |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | area analyzed by Compound discoverer (counts x seconds) | area analyzed by Compound discoverer (counts x seconds) |
Chromatography:
| Chromatography ID: | CH003485 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Thermo BETASIL Diol (150 x 2.1mm,5um) |
| Column Temperature: | 40 |
| Flow Gradient: | The LC program was as follow: starting at 93% B, to 40% B in 19 min, then to 0% B in 9 min, maintained at 0% B for 5 min, then back to 93% B in 3 min and re-equilibrated at 93% B for 9 min. |
| Flow Rate: | The flow rate was maintained at 0.15 mL/min, except for the first 30 seconds where the flow rate was uniformly ramped from 0.05 to 0.15 mL/ min. |
| Solvent A: | 20 mMAmmonium Carbonate, 0.1% Ammonium hydroxide, in Water |
| Solvent B: | Acetonitrile 97%, in water |
| Chromatography Type: | HILIC |
