DOI: 10.5061/dryad.dncjsxm91
title: Metabolic profiles of melanoma patients and PDX models

description: Patient-derived xenografts (PDXs) are frequently used as preclinical
 models, but their recapitulation of tumor metabolism in patients has not
 been closely examined. We developed a parallel workflow to analyze
 [U-13C]glucose tracing and metabolomics from patient melanomas and matched
 PDXs. Melanomas from patients have substantial TCA cycle labeling, similar
 to levels in human brain tumors. We observed differences in TCA cycle
 labelling among PDXs that were similar to differences we observed among
 the same melanomas in patients, but PDXs had higher labeling in glycolytic
 intermediates than the same melanomas in patients. We observed consistent
 metabolic alterations among PDXs and patient tumors that reflected
 species-specific differences in diet, enzyme expression and other factors.
 Despite these differences, most of nearly 200 PDXs retained a “metabolic
 fingerprint” that resembled the same melanomas in patients. PDX metabolism
 was also largely retained over at least 6 passages. We conclude that
 awareness of both high- and low-fidelity features will help optimize the
 use of PDXs to study human cancer metabolism.
description: # Metabolic profiles of melanoma patients and PDX models
 [https://doi.org/10.5061/dryad.dncjsxm91](https://doi.org/10.5061/dryad.dncjsxm91) ## Description of the data and file structure HILIC High Resolution Mass Spectrometry Metabolomics Data (two batches quantified from two separate runs): 1. metabolomics_sampleInfo_pairedSamples.xlsx and metabolomics_data_pairedSamples.xlsx are for paired patient tumor (P0) and early passage (P1) PDX. 2. metabolomics_sampleInfo_serialPassage.xlsx and metabolomics_data_serialPassage.xlsx for patient tumor (P0) and serially passaged (P1-6) PDX. Gas Chromatography Mass Spectrometry Data (for patient plasma, tumor, and PDX): Isotopologue Distributions for melanoma patient samples following [U-13C]Glucose infusion. Values are fractional enrichment, corrected for naturally occurring 13C carbon. 1. 13C_GlcTracing_Isotopologue_distribution_patient_plasma_data.xlsx: Plasma samples from patients at different timepoints during the in vivo [U-13C]Glucose infusion. 2. 13C_GlcTracing_Isotopologue_distribution_patient_data.xlsx: *NB MP1A, 1B, 1C were fragments of one lymph node (within further analyses, an average was used). 3. 13C_GlcTracing_Isotopologue_distribution_PDX_data.xlsx: Note suffix ("_X") denotes a fragment of a tumour, eg, NB8318_1, NB8318_2, and NB8318_3 represent three fragments from an individual subcutaneous tumour from a mouse with ID NB8318 By default, most infusions were 3h, with the exception being MP4A and MP10, where feasible, shorter infusions of 1h and 1 h 45 min, respectively, were performed (to match the duration in the patients) ### Files and variables #### File: metabolomics\_sampleInfo\_pairedSamples.xlsx **Description:** This file contains sample information for paired patient tumor (P0) and early passage (P1) PDX analyzed using HILIC high-resolution mass spectrometry. ##### Variables * Sample * Human/PDX * Patient * Primary/LN/Met.for.ANALYSIS * CategoricalSite * Bin.BRAF * BRAF.Mutation.(specific.if.known) * Pigment.Status * Sex #### File: metabolomics\_data\_pairedSamples.xlsx **Description:** This file contains metabolomics data for paired patient tumor (P0) and early passage (P1) PDX analyzed using HILIC high-resolution mass spectrometry. ##### Variables \[List of metabolites extracted – too long to show here fully. See below for details.] #### File: metabolomics\_sampleInfo\_serialPassage.xlsx **Description:** This file contains sample information for patient tumor (P0) and serially passaged (P1–6) PDX analyzed using HILIC high-resolution mass spectrometry. ##### Variables * Tube * Tumor.Name * Passage * Mouse.ID #### File: metabolomics\_data\_serialPassage.xlsx **Description:** This file contains metabolomics data for the patient tumor (P0) and serially passaged (P1–6) PDX analyzed using HILIC high-resolution mass spectrometry. ##### Variables \[List of metabolites extracted – too long to show here fully. See below for details.] #### File: 13C\_GlcTracing\_Isotopologue\_distribution\_patient\_plasma\_data.xlsx **Description:** Gas chromatography mass spectrometry data for isotopologue distributions in plasma samples collected from melanoma patients at different timepoints during [U-13C]Glucose infusions. Values are fractional enrichment, corrected for naturally occurring 13C carbon. ##### Variables * SampleID and Timepoints * Glucose M+0 through Glucose M+6 #### File: 13C\_GlcTracing\_Isotopologue\_distribution\_patient\_tumor\_data.xlsx **Description:** Gas chromatography mass spectrometry data for isotopologue distributions in melanoma patient tumors following [U-13C]Glucose infusions. Values are fractional enrichment, corrected for naturally occurring 13C carbon. Note: MP1A, MP1B, and MP1C were fragments of one lymph node, averaged in subsequent analyses. ##### Variables * Patient ID/Sample Name * Pyruvate_M0 through GLUCOSE_M6 (metabolite isotopologues with varying enrichment levels) #### File: 13C\_GlcTracing\_Isotopologue\_distribution\_PDX\_data.xlsx **Description:** Gas chromatography mass spectrometry data representing isotopologue distributions for melanoma patient-derived xenograft samples following [U-13C]Glucose infusion. Values are fractional enrichment, corrected for naturally occurring 13C carbon. Suffixes (e.g., "_X") denote fragments of a tumor. For example, NB8318_1, NB8318_2, and NB8318_3 represent three fragments from an individual subcutaneous tumor from a mouse with ID NB8318. ##### Variables * PDX/Passage * Sample Name/Mouse ID * 3PG_M0 through SUCCINATE_M4 (metabolite isotopologues with varying enrichment levels) ## Human subjects data All human data in this submission were collected with approval from the Institutional Review Boards of UT Southwestern Medical Center and the University of Michigan. Written informed consent was obtained from all participants, including consent to share de-identified data publicly for research purposes. All shared data have been de-identified according to HIPAA guidelines. Personal identifiers were removed, and only non-identifiable information such as age range, sex, and clinical characteristics is included. No data can be linked back to individual participants.