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Metadata and data files supporting 'FGFR4 overexpression and hotspot mutations in metastatic ER+ breast cancer are enriched in the lobular subtype'

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posted on 2019-06-28, 15:35 authored by Kevin M. Levine, Nolan Priedigkeit, Ahmed Basudan, Nilgun Tasdemir, Matthew J. Sikora, Ethan S. Sokol, Ryan J. Hartmaier, Kai Ding, Nedah Z. Ahmad, Rebecca J. Watters, Kurt R. Weiss, Jens-Uwe Blohmer, Carsten Denkert, Anna Machleidt, Maria M. Karsten, Michelle M Boisen, Esther Elishaev, Peter C. Lucas, Adrian V. Lee, Steffi Oesterreich
This data record describes the data files supporting the related publication "FGFR4 overexpression and hotspot mutations in metastatic ER+ breast cancer are enriched in the lobular subtype" and contains clinicopathologic, FGFR4 expression and FGFR4 hotspot mutation
allele frequency data files.

The related study investigates acquired resistance to endocrine therapy in Invasive lobular carcinoma (ILC); a common histological subtype in which most tumours are ER+ and so treated with endocrine therapy.

Study design summary
The related study is a subset analysis of existing RNA sequencing focusing only on ER+ patients treated with endocrine therapy prior to recurrence, and reporting additional FGFR4 expression data from paired gastrointestinal (GI) and ovarian metastases.

Sample size
26 patients. Treatment-naïve primary tumors and 29 endocrine-treated metastases, consisting of 7 bone, 7 brain, 5 GI, and 10 ovarian metastases were collected.


Data access:
For all data requests please contact:
Prof Steffi Oesterreich
Women’s Cancer Research Center
Magee Women’s Research Institute
Craft Avenue, Room B705
Pittsburgh, PA 15213, USA
Tel: 412-641-8555

Raw RNA-Seq data for the paired primary and metastatic samples will be made available upon request and under regulatory compliance via DUA

Data files and formats

Data supporting figure 1A:
files or repository identifiers: mm134_qpcr.xlsx, sum44_qpcr.xls
format: MS Excel
location of data file(s): Institutional file storage
data access: Contact Prof Oesterreich with data requests
description: FGFR4 expression in endocrine-resistant cell lines
see also: LTED and Tamoxifen resistant cell line expression data below

Data supporting figure 1B:
files or repository identifiers: Supplementary Table S1.xlsx
format: MS Excel
location of data file(s): figshare (this data record)
data access: publicly accessible
description: FGFR4 Expression in Paired ER+
Endocrine−Treated Breast Metastases
see also: section on RNA-Seq expression

Data supporting figure 2A-D:
files or repository identifiers: FGFR4_allVUS_3_13_2018.csv
format: CSV text file
location of data file(s): institutional file storage
data access: contact Prof Oesterreich with data requests
see also: FGFR4 mutations data below
description: FGFR4 mutations in breast metastases, FGFR4 hotspot mutations (N535, V550) in breast metastases vs non-breast metastases, FGFR4 hotspot mutations in metastatic IDC vs metastatic ILC and FGFR4 hotspot mutations in endocrine-treated metastases

Data supporting supplementary material:
files or repository identifiers: IHC_image_ranks.xlsx
format: MS Excel
location of data file(s): institutional file storage
data access: contact Prof Oesterreich with data requests
see also: FGFR4 expression in RATHER data below
description: FGFR4 antibody validation in engineered Sum44PE cells, FGFR4 RNA and protein correlation based on querying of the RATHER consortium microarray and RPPA data of ILC primary tumors.

LTED and Tamoxifen resistant cell line expression:
files or repository identifiers: GSE12708, GSE75971, GSE116744
format: CEL, TXT text file, CSV text file
location of data file(s): NCBI Gene Expression Omnibus
data access: publicly shared at the GEO repository. GSE75971,GSE116744 also available in shiny app format at https://leeoesterreich.org/resources
description: RNA-Sequencing data on long-term estrogen deprived (LTED) cell lines (GSE116744, GSE75971) and microarray analysis data on tamoxifen resistant cell lines (GSE75971)

RNA-Seq expression
files or repository identifiers: metPairs_endoTreated_log2CPM.Rda, 55 raw transcript count files (BO_1M.ts.count.0.8.2, etc)
format: R data frame, TXT text files
data access: publicly accessible
description: log2 TMM-normalized CPM for all endocrine-treated metastases, and transcript counts

FGFR4 expression in RATHER:
files or repository identifiers: GSE68057
format: TXT text file
location of data file(s): NCBI Gene Expression Omnibus
data access: publicly accessible
description: Microarray based gene expression for invasive lobular cancer samples; part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium.

FGFR4 expression in paired samples:
files or repository identifiers: Supplementary Table S1.xlsx
format: MS Excel
location of data file(s): figshare (this data record)
data access: publicly accessible
description: Clinicopathologic data and FGFR4 expression for matched primary: metastatic tumors

FGFR4 hotspot mutations in MSK-IMPACT:
files or repository identifiers: Supplementary Table S2.xlsx
format: MS Excel
location of data file(s): figshare (this data record)
data access: publicly accessible
description: Clinicopathologic data and FGFR4 hotspot mutation allele frequencies from MSK-IMPACT

FGFR4 mutations
files or repository identifiers: brca_igr_2015 (Lefebvre et al.), breast_msk_2018 (MSK-IMPACT), MCTP (MET500)
format: websites
data access: publicly accessible
description: FGFR4 hotspots (N535 and V550) queried in Lefebvre et al. and MSK-IMPACT using the cBio portal, and MET500 using the MET500 portal.

The data in FGFR4_allVUS_3_13_2018.csv was accessible to the authors through a DUA with Foundation Medicine- (as approved by Western Institutional Review Board). This data will not be made publicly available in order to protect patient privacy.

Collection and analysis of tumor specimens was approved under the University of Pittsburgh (distant metastases) and Charite Universitaetsmedizin Berlin IRB (paired local recurrence) guidelines. Additional patient details will not be made publicly available to protect patient privacy.

Funding

FGFR4: A druggable mediator of endocrine resistance in breast cancer

National Cancer Institute

Find out more...

This work was supported by the Breast Cancer Research Foundation [AVL and SO]; Susan G. Komen Scholar awards [SAC110021 to AVL, SAC160073 to SO]; the Metastatic Breast Cancer Network [SO]; the National Cancer Institute [R01CA224909 to SO, 5F30CA203154 to KML, 5F30CA203095 to NP,]; and the Fashion Footwear Association of New York, Magee-Women’s Research Institute and Foundation, Nicole Meloche Foundation, Penguins Alumni Foundation, and the Shear Family Foundation. SO and AVL are Hillman Fellows. Research reported in this publication was also supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM008208 (KML and NP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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    Keywords

    breast cancerInvasive lobular carcinomaILCER+estrogen receptor-positive breast cancersubset analysisendocrine therapygastrointestinal metastasesovarian metastasesFGFR4FGFR4 expressionendocrine resistancehotspot mutationsmetastatic breast cancerFGFR4 overexpressionlong-term estrogen deprived cell lines

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