ArticleCold Spring Harbor molecular case studies2016
Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer.
Article in Cold Spring Harbor molecular case studies, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Phylogeography of Bone Metastasis: Clonal Evolution, Skeletal Niche Adaptation, and Clinical Implications.International journal of molecular sciences · 2026Review
- Blood and urine-based biomarkers in prostate cancer: Current advances, clinical applications, and future directions.The journal of liquid biopsy · 2025Review
- MODA: a graph convolutional network-based multi-omics integration framework for unraveling hub molecules and disease mechanisms.Briefings in bioinformatics · 2025Article
- Overexpression of PIK3CG in Cancer Cells Promotes Lung Cancer Cell Migration and Metastasis Through Enhanced MMPs Expression and Neutrophil Recruitment and Activation.Biochemical genetics · 2025Article
- Clonal phylogenies inferred from bulk, single cell, and spatial transcriptomic analysis of epithelial cancers.PloS one · 2025Article
- Circulating tumor cell markers for early detection and drug resistance assessment through liquid biopsy.Frontiers in oncology · 2025Review
- A comprehensive analysis of the tryptophan metabolism-related gene signature to predict the prognosis of esophageal squamous cell carcinoma based on multi-omics.Frontiers in molecular biosciences · 2025Article
- Prediction of immunotherapy response using mutations to cancer protein assemblies.Science advances · 2024Article
- Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting.Acta neuropathologica communications · 2023Article
- Cancer origin tracing and timing in two high-risk prostate cancers using multisample whole genome analysis: prospects for personalized medicine.Genome medicine · 2023Article
- PTPRD and CNTNAP2 as markers of tumor aggressiveness in oligodendrogliomas.Scientific reports · 2022Article
- Article
- Review
- Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy.Nature communications · 2020Article
- Article
- Detection of Molecular Signatures of Homologous Recombination Deficiency in Prostate Cancer with or without BRCA1/2 Mutations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Screening key miRNAs and genes in prostate cancer by microarray analysis.Translational cancer research · 2020Article
- Function, Regulation and Biological Roles of PI3Kγ Variants.Biomolecules · 2019Review
- Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications.Medicines (Basel, Switzerland) · 2019Review
- VPS34 complexes from a structural perspective.Journal of lipid research · 2019Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report the first combined analysis of whole-genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole-genome and transcriptome sequence was obtained from nine anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 yr before death. Transcriptome analysis revealed increased expression of androgen receptor (AR)-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only one of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today, given this knowledge, the use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations may be critical for effective actionability and merit further study. Our findings suggest that a large set of deeply analyzed cases could serve as a powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials.
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