{"entity": "publication", "iuid": "8122218c94514e5d8795dfa4cf4ace6a", "timestamp": "2026-08-22T06:57:33.959Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8122218c94514e5d8795dfa4cf4ace6a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8122218c94514e5d8795dfa4cf4ace6a"}}, "title": "Integrative genomic and transcriptomic analyses illuminate the ontology of HER2-low breast carcinomas.", "authors": [{"family": "Berrino", "given": "Enrico", "initials": "E"}, {"family": "Annaratone", "given": "Laura", "initials": "L"}, {"family": "Bellomo", "given": "Sara Erika", "initials": "SE"}, {"family": "Ferrero", "given": "Giulio", "initials": "G"}, {"family": "Gagliardi", "given": "Amedeo", "initials": "A"}, {"family": "Bragoni", "given": "Alberto", "initials": "A"}, {"family": "Grassini", "given": "Dora", "initials": "D"}, {"family": "Guarrera", "given": "Simonetta", "initials": "S"}, {"family": "Parlato", "given": "Caterina", "initials": "C"}, {"family": "Casorzo", "given": "Laura", "initials": "L"}, {"family": "Panero", "given": "Mara", "initials": "M"}, {"family": "Sarotto", "given": "Ivana", "initials": "I"}, {"family": "Giordano", "given": "Silvia", "initials": "S"}, {"family": "Cereda", "given": "Matteo", "initials": "M"}, {"family": "Montemurro", "given": "Filippo", "initials": "F"}, {"family": "Ponzone", "given": "Riccardo", "initials": "R"}, {"family": "Crosetto", "given": "Nicola", "initials": "N"}, {"family": "Naccarati", "given": "Alessio", "initials": "A"}, {"family": "Sapino", "given": "Anna", "initials": "A"}, {"family": "Marchi\u00f2", "given": "Caterina", "initials": "C", "orcid": "0000-0003-2024-6131", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ab9a52c7f9fe4aeea5cc5a35d4c05e0c.json"}}], "type": "journal article", "published": "2022-08-29", "journal": {"title": "Genome Med", "issn": "1756-994X", "volume": "14", "issue": "1", "pages": "98", "issn-l": "1756-994X"}, "abstract": "The \"HER2-low\" nomenclature identifies breast carcinomas (BCs) displaying a HER2 score of 1+/2+ in immunohistochemistry and lacking ERBB2 amplification. Whether HER2-low BCs (HLBCs) constitute a distinct entity is debated.\n\nWe performed DNA and RNA high-throughput analysis on 99 HLBC samples (n = 34 cases with HER2 score 1+/HLBC-1, n = 15 cases with HER2 score 2+ and ERBB2 not amplified/HLBC-2N, and n = 50 cases with score 2+ and ERBB2 copy number in the equivocal range/HLBC-2E). We compared the mutation rates with data from 1317 samples in the Memorial Sloan-Kettering Cancer Center (MSKCC) BC cohort and gene expression data with those from an internal cohort of HER2-negative and HER2-positive BCs.\n\nThe most represented mutations affected PIK3CA (31/99, 31%), GATA3 (18/99, 18%), TP53 (17/99, 17%), and ERBB2 (8/99, 8%, private to HLBC-2E). Tumor mutational burden was significantly higher in HLBC-1 compared to HLBC-2E/N (P = 0.04). Comparison of mutation spectra revealed that HLBCs were different from both HER2-negative and HER2-positive BCs, with HLBC-1 resembling more HER2-negative tumors and HLBC-2 mutationally related to HER2-addicted tumors. Potentially actionable alterations (annotated by using OncoKB/ESCAT classes) affected 52 patients. Intra-group gene expression revealed overlapping features between HLBC-1 and control HER2-negative BCs, whereas the HLBC-2E tumors showed the highest diversity overall. The RNA-based class discovery analysis unveiled four subsets of tumors with (i) lymphocyte activation, (ii) unique enrichment in HER2-related features, (iii) stromal remodeling alterations, and (iv) actionability of PIK3CA mutations (LAURA classification).\n\nHLBCs harbor distinct genomic features when compared with HER2-positive and HER2-negative BCs; however, differences across IHC classes were also unveiled thus dissecting the full picture of heterogeneity across HER2-low disease. The HLBC-2E category harbors most distinctive features, whereas HLBC-1 seems superimposable to HER2-negative disease. Further studies are needed to ascertain whether the four genomic-driver classes of the LAURA classification hold prognostic and/or predictive implications.", "doi": "10.1186/s13073-022-01104-z", "pmid": "36038884", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9426037"}, {"db": "pii", "key": "10.1186/s13073-022-01104-z"}], "notes": [], "created": "2026-08-21T12:40:35.537Z", "modified": "2026-08-21T12:40:35.615Z"}