ArticleCancer discovery2022
Loss of Epigenetic Regulation Disrupts Lineage Integrity, Induces Aberrant Alveogenesis, and Promotes Breast Cancer.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
- LC-MS/MS-based clinical value exploration of the methionine cycle in luminal breast cancer.Oncology letters · 2026Article
- Breast cancer prevention by prophylactic Lalba mRNA-LNP vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- The Great Escape: the systems biology of endocrine resistance and lineage plasticity.Endocrine-related cancer · 2026Review
- Temporal control of sgRNA library activation unlocks large-scale in vivo CRISPR screens.Cell reports methods · 2026Article
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- Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.Nature reviews. Cancer · 2026Review
- Branching out: the diverse roles of stem and progenitor cells in mammary gland development.Journal of mammary gland biology and neoplasia · 2026Review
- Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis.Nature communications · 2026Article
- FOXA1 mutations co-opt nascent transcription factor networks in partnership with androgen receptor to enhance prostate tumorigenicity.Cell reports · 2026Article
- Expression Patterns of LALBA and Nucleolin and Their Clinical, Prognostic, and Immune Relevance in Breast Cancer Tissues of Mexican Patients.International journal of molecular sciences · 2026Article
- Divergent aging of nulliparous and parous mammary glands reveals IL33+ hybrid epithelial cells.Nature communications · 2026Article
- EML4-ALK Variant-Specific Genetic Interactions Shape Lung Tumorigenesis.Cancer discovery · 2026Article
- BRCA1: An Unrecognized Modulator of Lineage Plasticity in Basal-like Breast Cancer.Journal of mammary gland biology and neoplasia · 2025Review
- Functional Mapping of Epigenomic Regulators Uncovers Coordinated Tumor Suppression by the HBO1 and MLL1 Complexes.Cancer discovery · 2025Article
- Review
- Topoisomerase IIb binding delineates localized mutational processes and driver mutations in cancer genomes.Nature communications · 2025Article
- Methods and applications of in vivo CRISPR screening.Nature reviews. Genetics · 2025Review
- GPD1L as a potential biomarker associated with Treg cell infiltration and lipid metabolism in clear cell renal cell carcinoma.Journal of translational medicine · 2025Article
- Intraductal Injection of Adenoviruses to Perform Lineage Tracing in the Mammary Gland.Journal of mammary gland biology and neoplasia · 2025Review
Corrections and comments
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Authors and funding
36 authors at 8 institutions in 4 countries.
Funding
Abstract
Systematically investigating the scores of genes mutated in cancer and discerning disease drivers from inconsequential bystanders is a prerequisite for precision medicine but remains challenging. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to study 215 recurrent "long-tail" breast cancer genes, which revealed epigenetic regulation as a major tumor-suppressive mechanism. We report that components of the BAP1 and COMPASS-like complexes, including KMT2C/D, KDM6A, BAP1, and ASXL1/2 ("EpiDrivers"), cooperate with PIK3CAH1047R to transform mouse and human breast epithelial cells. Mechanistically, we find that activation of PIK3CAH1047R and concomitant EpiDriver loss triggered an alveolar-like lineage conversion of basal mammary epithelial cells and accelerated formation of luminal-like tumors, suggesting a basal origin for luminal tumors. EpiDriver mutations are found in ∼39% of human breast cancers, and ∼50% of ductal carcinoma in situ express casein, suggesting that lineage infidelity and alveogenic mimicry may significantly contribute to early steps of breast cancer etiology. SIGNIFICANCE: Infrequently mutated genes comprise most of the mutational burden in breast tumors but are poorly understood. In vivo CRISPR screening identified functional tumor suppressors that converged on epigenetic regulation. Loss of epigenetic regulators accelerated tumorigenesis and revealed lineage infidelity and aberrant expression of alveogenesis genes as potential early events in tumorigenesis. This article is highlighted in the In This Issue feature, p. 2711.
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Registered trials
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.