ArticleThe Journal of clinical investigation2020
Genomic landscape of metastatic breast cancer identifies preferentially dysregulated pathways and targets.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Investigating the shared genetic architecture of uterine leiomyoma and breast cancer: A genome-wide cross-trait analysis.American journal of human genetics · 2022Pooled it
- Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial.Nature medicine · 2025Trial
- Multi-omic Profiling of Recurrence Risk Across Breast Cancer Subtypes.medRxiv : the preprint server for health sciences · 2026Article
- Genomic and transcriptomic evaluation of primary and recurrent luminal B-like breast cancer.ESMO open · 2026Article
- Review
- Residual Breast Cancer Cells Co-opt SOX5-Driven Endochondral Ossification to Maintain Dormancy.Cancer discovery · 2026Article
- Adipocyte-driven STAT3-ANGPT2-PTGIS axis promotes cutaneous metastasis in breast cancer and represents a targetable pathway.NPJ precision oncology · 2026Article
- Treating T24 cells with erianin restores gefitinib drug sensitivity by regulating MYLK to inhibit EGFR and EMT processes.American journal of cancer research · 2026Article
- Biomarker testing in advanced or metastatic hormone receptor-positive, human epidermal growth factor receptor 2 negative breast cancer: expert recommendations.Therapeutic advances in medical oncology · 2026Review
- Endocrine disruption to metastasis: How phthalates promote breast carcinogenesis.Ecotoxicology and environmental safety · 2025Review
- The mTORC2 subunit RICTOR drives breast cancer progression by promoting ganglioside biosynthesis through transcriptional and epigenetic mechanisms.PLoS biology · 2025Article
- Signature of leukemia stem cell death pattern predicts prognosis and therapeutic response of acute myeloid leukemia patients.Scientific reports · 2025Article
- Characterization of extracellular vesicle-associated DNA and proteins derived from organotropic metastatic breast cancer cells.Journal of experimental & clinical cancer research : CR · 2025Article
- CD44 Marks Dormant Tumor Cells After HER2 Inhibition in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Shared Genetic Architecture and Causal Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density.The Journal of clinical endocrinology and metabolism · 2025Article
- PAQR5 drives the malignant progression and shapes the immunosuppressive microenvironment of hepatocellular carcinoma by activating the NF-κB signaling.Biomarker research · 2025Article
- Comprehensive mapping elucidates high risk genotypes in primary metastatic breast cancer.Neoplasia (New York, N.Y.) · 2025Article
- Role of immune cell homeostasis in research and treatment response in hepatocellular carcinoma.Clinical and experimental medicine · 2025Article
- Distant Metastases of Breast Cancer Resemble Primary Tumors in Cancer Cell Composition but Differ in Immune Cell Phenotypes.Cancer research · 2025Article
- Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma.Blood cancer journal · 2024Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Nearly all breast cancer deaths result from metastatic disease. Despite this, the genomic events that drive metastatic recurrence are poorly understood. We performed whole-exome and shallow whole-genome sequencing to identify genes and pathways preferentially mutated or copy-number altered in metastases compared with the paired primary tumors from which they arose. Seven genes were preferentially mutated in metastases - MYLK, PEAK1, SLC2A4RG, EVC2, XIRP2, PALB2, and ESR1 - 5 of which are not significantly mutated in any type of human primary cancer. Four regions were preferentially copy-number altered: loss of STK11 and CDKN2A/B, as well as gain of PTK6 and the membrane-bound progesterone receptor, PAQR8. PAQR8 gain was mutually exclusive with mutations in the nuclear estrogen and progesterone receptors, suggesting a role in treatment resistance. Several pathways were preferentially mutated or altered in metastases, including mTOR, CDK/RB, cAMP/PKA, WNT, HKMT, and focal adhesion. Immunohistochemical analyses revealed that metastases preferentially inactivate pRB, upregulate the mTORC1 and WNT signaling pathways, and exhibit nuclear localization of activated PKA. Our findings identify multiple therapeutic targets in metastatic recurrence that are not significantly mutated in primary cancers, implicate membrane progesterone signaling and nuclear PKA in metastatic recurrence, and provide genomic bases for the efficacy of mTORC1, CDK4/6, and PARP inhibitors in metastatic breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.