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) |
MS:
| MS ID: | MS004378 |
| Analysis ID: | AN004631 |
| Instrument Name: | Thermo Orbitrap ID-X tribrid |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Data was acquired on the ID-X in switching polarities at 120000 resolution, with an AGC target of 1e5, and a m/z range of 65 to 1000. MS1 data is acquired in switching polarities for all samples. Data is analyzed in Compound Discoverer 3.3 (CD, ThermoFisher Scientific). A mix of standard of each target was run along the samples and used as the unlabeled reference for the CD labelling workflow. Isotopomer distribution is found in the exchange column, as % of 0 labelled carbon, 1 labelled carbon, 2 labelled carbon, etc. Those are corrected for natural abundance. For the compounds that couldn’t be analyzed by CD, the areas have been extracted with Tracefinder manually. |
| Ion Mode: | POSITIVE |
| MS ID: | MS004379 |
| Analysis ID: | AN004632 |
| Instrument Name: | Thermo Orbitrap ID-X tribrid |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | Data was acquired on the ID-X in switching polarities at 120000 resolution, with an AGC target of 1e5, and a m/z range of 65 to 1000. Data is analyzed in Compound Discoverer 3.3 (CD, ThermoFisher Scientific). A mix of standard of each target was run along the samples and used as the unlabeled reference for the CD labelling workflow. Isotopomer distribution is found in the exchange column, as % of 0 labelled carbon, 1 labelled carbon, 2 labelled carbon, etc. Those are corrected for natural abundance. For the compounds that couldn’t be analyzed by CD, the areas have been extracted with Tracefinder manually. |
| Ion Mode: | NEGATIVE |
