Metadata supporting the article: Characterizing Advanced Breast Cancer Heterogeneity and Treatment Resistance through Serial Biopsies and Comprehensive Analytics
Creators: name: Li, Allen
name: Keck, Jamie M.
name: Swapnil Parmar
name: Patterson, Janice
name: Labrie, Marilyne
name: Creason, Allison L.
name: Johnson, Brett E.
name: Downey, Molly
name: Thomas, George
name: Beadling, Carol
name: Heiser, Laura M.
name: Kolodzie, Annette
name: Guimaraes, Alexander R.
name: Corless, Christopher L
name: Gray, Joe W
name: Mills, Gordon B
name: Bergan, Raymond C
name: Mitri, Zahi I
Publisher: name: figshare
Year: 2021
Subjects: subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Biological Techniques
subject: Cancer
subject: 111203 Cancer Genetics
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 111201 Cancer Cell Biology
subject: 60405 Gene Expression (incl. Microarray and other genome-wide approaches)

description: Molecular heterogeneity in metastatic breast cancer presents multiple clinical challenges in accurately characterizing and treating the disease. Current diagnostic approaches offer limited ability to assess heterogeneity that exists among multiple metastatic lesions throughout the treatment course. In this study, the authors developed a precision oncology platform that combines serial biopsies, multi-omic analysis, longitudinal patient monitoring, and molecular tumor boards, with the goal of improving cancer management through enhanced understanding of the entire cancer ecosystem within each patient.<br><b>Data access</b>: The raw RNA sequencing data generated during the current study, are available in the dbGaP repository: <b>https://identifiers.org/dbgap:phs002321.v1.p1</b>. As these files are controlled access, researchers must request access to the dbGaP data. The repository also includes clinical and phenotypic metadata and molecular data (including gene and protein expression). The normalized gene expression (RNAseq) data and the reverse phase protein array data (protein expression data), are publicly available in the Synapse repository under the following project accession: <b>syn22975916</b>. HER2 immunohistochemistry data, Intracellular Signaling Protein Panel assay data, and data from the GeneTrails Solid Tumor Panel assay, are not publicly available, but will be made available on reasonable request. Please contact the Knight Diagnostic Laboratories at Oregon Health and Science University (OHSU), email: <b>KDLClientServices@ohsu.edu</b>, for more information on these datasets. The TCGA RNAseq data and the TCGA RPPA analysed during the study, are available in the Open Science Framework repository: <b>https://osf.io/gqrz9/</b>.<br><b>Study approval and patient consent</b>: Specimens and data were acquired from the participant by obtaining informed written consent to use their coded de-identified data and/or specimens for research and publication purpose under regulation by the Oregon Health &amp; Science University (OHSU) IRB# 16113 Molecular Mechanisms of Tumor Evolution and Resistance to Therapy (MMTERT).<br><b>Study aims and methodology</b>: The mechanisms underlying intermetastatic heterogeneity (IMH) and the evolutionary paths of metastatic lesions in individual patients remain poorly understood. There is no routine clinical assays or reliable predictive models for consistently assessing IMH throughout the disease course and under therapeutic pressure. Because of the effect of IMH on prognosis and treatment resistance, there is a compelling need to develop a reliable means for assessing IMH in clinical settings to enable rational modification or addition of therapy. In this study, the authors discuss the importance of repeat metastatic biopsies in capturing clinically significant IMH and this program’s multi-omic translational oncology approach in an individual breast cancer patient, with a focus on understanding the role of IMH in treatment response. The following procedures and assays are described in more detail in the related article: patient enrollment, tissue processing, and DNA extraction, immunohistochemistry, NGS: GeneTrails® Comprehensive Solid Tumor Panel assay, RNA transcriptome sequencing, RNA expression profiling, PAM50 intrinsic subtyping/TNBC-specific intrinsic subtyping, Intracellular Signaling Protein Panel assay, Reverse phase protein array, and protein pathway analysis.<br> <b>Data supporting the figures and tables in the article</b> (Please see the Data access section above for information on data access conditions and links to publicly available data):Data supporting figure 2: <b>HER2 immunohistochemistry data</b>. The clinical immunohistochemistry was performed by a CLIA/CAP laboratory and the HER2 IHC results taken from a clinical pathology report. <br>Data supporting figure 3: <b>Intracellular Signaling Protein Panel data</b>. This assay was performed in a CLIA/CAP laboratory and the data was taken from the clinical Intracellular Signaling Protein Panel report.<br>Data supporting figure 4: <b>RNA prolifing/ intrinsic subtyping data</b> (Normalized_Gene_Expression.tsv file, in .tsv file format), <b>RNA prolifing / gene expression data</b> (fastq files).<br>Data supporting figure 5: <b>RPPA prolifing data</b>: RPPA_Level2.csv, RPPA_Level3.csv, RPPA_Level4.csv, in .csv file format. RPPA prolifing data are also in dbGaP, in csv file format.<br>Data supporting table 1: <b>Genomic alterations data</b>. The clinical GeneTrails Solid Tumor Panel was performed within a CLIA/CAP laboratory and taken from the clinical report.<br>