Whole-Genome Landscape of Breast Cancers from India shows Distinct Clinically Actionable Subtypes
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Le résumé fourni par la source
Abstract Breast cancer remains the leading cause of cancer-related mortality among women globally, yet South Asian populations are critically underrepresented in genomic studies. Here, we present whole-genome and transcriptome analyses of over 500 treatment-naïve, clinically annotated breast tumors from India, representing the first large-scale integrative omics characterization of this population. In addition to established drivers, we identify novel significantly mutated genes, including ISM2 , TERF2 , and DHRSX , under positive selection, along with previously unreported potentially pathogenic somatic variants. Notably, the distribution of key hotspot mutations appears shaped by immune escape pressures. We uncover recurrent copy number alterations driving lipid metabolic reprogramming (e.g., NCEH1 and PLD1 amplifications) and complex structural events, including IKZF3 promoter hijacking leading to ERBB2 overexpression and TTC28 -associated genomic instability—findings not previously described in breast cancer. Mutational processes are dominated by DNA repair deficiency, APOBEC activity, and genome instability. We identify three genomic features significantly associated with poor post-surgical recurrence-free survival. Transcriptomic profiling reveals distinct intrinsic subtypes with divergent immune landscapes, including a high-risk HER2-androgenic cluster with the worst outcomes. Additionally, we find a novel transcriptomic signature that robustly captures a HER2-like transcriptional state within triple-negative breast cancer patients – with major implications for TNBC treatment. Finally, clinically actionable germline and somatic alterations are revealed with high significance, highlighting opportunities for therapeutic repurposing. Together, the study establishes a comprehensive molecular atlas of breast cancer in an underrepresented population, providing critical insights into tumour biology and advancing precision oncology.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Whole-Genome Landscape of Breast Cancers from India shows Distinct Clinically Actionable Subtypes
- Date Crossref
- 30/03/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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Institute of Genomics and Integrative Biology Integrative and Functional Biology Unit pays non établi dans la noticeStructure de recherche
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National Institute of Biomedical Genomics pays non établi dans la noticeÉtablissement de santé
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Krishna Institute of Medical Sciences Deemed University pays non établi dans la noticeUniversité ou école supérieure
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Saroj Gupta Cancer Centre & Research Institute pays non établi dans la noticeÉtablissement de santé
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Shaqra University pays non établi dans la noticeUniversité ou école supérieure
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All India Institute of Medical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Rajiv Gandhi Cancer Institute and Research Centre pays non établi dans la noticeÉtablissement de santé
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Indian Institute of Chemical Biology pays non établi dans la noticeStructure de recherche
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Institute of Microbial Technology pays non établi dans la noticeStructure de recherche
Integrative and Functional Biology Unit — Institute of Genomics and Integrative Biology, National Institute of Biomedical Genomics et Centre for Cellular and Molecular Biology, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.