{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shah OS"],"funding":["Breast Cancer Research Foundation (BCRF)","Breast Cancer Research Foundation","American Society of Clinical Oncology","HHS | NIH | National Cancer Institute","NCI NIH HHS","American Society of Clinical Oncology (ASCO)","The Dynami Foundation","NIH HHS"],"pagination":["e2322068121"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11295029"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["121(31)"],"pubmed_abstract":["Mixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive ductal and E-cadherin negative lobular morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct morphologies also have distinct biology and risk of recurrence. Our spatially resolved transcriptomic, genomic, and single-cell profiling revealed clinically significant differences between ductal and lobular tumor regions including distinct intrinsic subtype heterogeneity - e.g., MDLC with triple-negative breast cancer (TNBC) or basal ductal and estrogen receptor positive (ER+) luminal lobular regions, distinct enrichment of cell cycle arrest/senescence and oncogenic (ER and <i>MYC</i>) signatures, genetic and epigenetic <i>CDH1</i> inactivation in lobular but not ductal regions, and single-cell ductal and lobular subpopulations with unique oncogenic signatures further highlighting intraregional heterogeneity. Altogether, we demonstrated that the intratumoral morphological/histological heterogeneity within MDLC is underpinned by intrinsic subtype and oncogenic heterogeneity which may result in prognostic uncertainty and therapeutic dilemma."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Spatial molecular profiling of mixed invasive ductal and lobular breast cancers reveals heterogeneity in intrinsic molecular subtypes, oncogenic signatures, and mutations."],"pmcid":["PMC11295029"],"funding_grant_id":["P30 CA047904","S10 OD028483","P30 CA008748","P50 CA247749","xxxxxxxxxxxxxx"],"pubmed_authors":["Pareja F","Dopeso H","Johnston TJ","Mandelker D","Lee AV","Kleer CG","Weigelt B","Atkinson JM","Lucas PC","Shah OS","McAuliffe PF","Bhargava R","Foldi J","Oesterreich S","Reis-Filho JS","da Silva EM","Nasrazadani A","Selenica P","Stallaert W"],"additional_accession":[]},"is_claimable":false,"name":"Spatial molecular profiling of mixed invasive ductal and lobular breast cancers reveals heterogeneity in intrinsic molecular subtypes, oncogenic signatures, and mutations.","description":"Mixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive ductal and E-cadherin negative lobular morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct morphologies also have distinct biology and risk of recurrence. Our spatially resolved transcriptomic, genomic, and single-cell profiling revealed clinically significant differences between ductal and lobular tumor regions including distinct intrinsic subtype heterogeneity - e.g., MDLC with triple-negative breast cancer (TNBC) or basal ductal and estrogen receptor positive (ER+) luminal lobular regions, distinct enrichment of cell cycle arrest/senescence and oncogenic (ER and <i>MYC</i>) signatures, genetic and epigenetic <i>CDH1</i> inactivation in lobular but not ductal regions, and single-cell ductal and lobular subpopulations with unique oncogenic signatures further highlighting intraregional heterogeneity. Altogether, we demonstrated that the intratumoral morphological/histological heterogeneity within MDLC is underpinned by intrinsic subtype and oncogenic heterogeneity which may result in prognostic uncertainty and therapeutic dilemma.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-06-02T04:20:18.923Z","creation":"2025-04-03T23:36:44.674Z"},"accession":"S-EPMC11295029","cross_references":{"pubmed":["39042692"],"doi":["10.1073/pnas.2322068121"]}}