{"doi":"10.1101/2022.10.07.511231","title":"A Novel Mouse Model that Recapitulates the Heterogeneity of Human Triple Negative Breast Cancer","abstract":"Abstract Triple-negative breast cancer (TNBC) patients have a poor prognosis and few treatment options. Mouse models of TNBC are important for development of new targeted therapies, but few TNBC mouse models exist. Here, we developed a novel TNBC murine model by mimicking two common TNBC mutations with high co-occurrence: amplification of the oncogene MYC and deletion of the tumor suppressor PTEN. This Myc;Ptenfl murine model develops TN mammary tumors that display histological and molecular features commonly found in human TNBC. We performed deep omic analyses on Myc;Ptenfl tumors including machine learning for morphologic features, bulk and single-cell RNA-sequencing, multiplex immunohistochemistry and single-cell phenotyping. Through comparison with human TNBC, we demonstrated that this new genetic mouse model develops mammary tumors with differential survival that closely resemble the inter- and intra-tumoral and microenvironmental heterogeneity of human TNBC; providing a unique pre-clinical tool for assessing the spectrum of patient TNBC biology and drug response. Statement of significance The development of cancer models that mimic triple-negative breast cancer (TNBC) microenvironment complexities is critical to develop effective drugs and enhance disease understanding. This study addresses a critical need in the field by identifying a murine model that faithfully mimics human TNBC heterogeneity and establishing a foundation for translating preclinical findings into effective human clinical trials.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304539,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9258,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":536438,"name":"Xiaoyan Wang","orcid":"0000-0002-7333-4074","position":1,"is_corresponding":false},{"id":585499,"name":"Nicholas L. Calistri","orcid":"0000-0002-8541-0919","position":2,"is_corresponding":false},{"id":645766,"name":"Jennifer Eng","orcid":"0000-0003-1499-8417","position":3,"is_corresponding":false},{"id":559200,"name":"Colin J. Daniel","orcid":"0009-0008-1915-3660","position":4,"is_corresponding":false},{"id":997427,"name":"Luke Ternes","orcid":"0000-0002-7739-0292","position":5,"is_corresponding":false},{"id":935132,"name":"Eun Na Kim","orcid":"0000-0003-2992-7881","position":6,"is_corresponding":false},{"id":778119,"name":"Carl Pelz","orcid":"0000-0002-2235-880X","position":7,"is_corresponding":false},{"id":574404,"name":"Michael W. Munks","orcid":"0000-0002-0335-7238","position":8,"is_corresponding":false},{"id":225125,"name":"Courtney B. Betts","orcid":"0000-0002-0432-0445","position":9,"is_corresponding":false},{"id":997428,"name":"Nell Kirchberger","orcid":"0009-0003-7024-705X","position":10,"is_corresponding":false},{"id":479853,"name":"Sunjong Kwon","orcid":null,"position":11,"is_corresponding":false},{"id":513739,"name":"Elmar Bucher","orcid":"0000-0002-2929-2460","position":12,"is_corresponding":false},{"id":649439,"name":"Xi Li","orcid":"0000-0001-9185-7728","position":13,"is_corresponding":false},{"id":997429,"name":"Trent Waugh","orcid":"0009-0001-0874-1482","position":14,"is_corresponding":false},{"id":620650,"name":"Jennifer A. Pietenpol","orcid":"0000-0001-6268-6798","position":15,"is_corresponding":false},{"id":34060,"name":"Melinda E. Sanders","orcid":"0000-0001-7227-1764","position":16,"is_corresponding":false},{"id":997971,"name":"Gordon Mills","orcid":null,"position":17,"is_corresponding":false},{"id":225142,"name":"Koei Chin","orcid":"0000-0001-8061-7462","position":18,"is_corresponding":false},{"id":225135,"name":"Young Hwan Chang","orcid":"0000-0001-8764-1959","position":19,"is_corresponding":false},{"id":90464,"name":"Lisa M. Coussens","orcid":"0000-0003-2389-1865","position":20,"is_corresponding":false},{"id":225103,"name":"Joe W. Gray","orcid":"0000-0001-9225-6756","position":21,"is_corresponding":false},{"id":1893,"name":"Laura M. Heiser","orcid":"0000-0003-3330-0950","position":22,"is_corresponding":false},{"id":284346,"name":"Rosalie C. Sears","orcid":"0000-0003-1558-2413","position":23,"is_corresponding":false},{"id":997426,"name":"Zinab O. Doha","orcid":"0000-0003-2952-9840","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T00:32:32.651796Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}