{
  "abstract": "Triple-negative breast cancer (TNBC) is more prevalent in women of sub-Saharan African (SSA) than European (EUR) ancestry. Despite ancestry-related heterogeneity remaining neglected in cancer research, its evaluation can reveal useful insights on essential pathways underlying complex diseases. High-throughput data (DepMap and GDSC) were mined by performing differential analyses (gene essentiality and drug sensitivity, respectively) between SSA and EUR TNBC cell lines. BLM and interacting genes (RMI1, RMI2, TOP3A) showed greater essentiality in SSA than in EUR TNBC cell lines. SSA TNBC patients and cancer cell lines tended to have a lower median BLM expression than EUR counterparts, and its expression was positively correlated with structural mutations in tumour cells. Concordantly, BLM expression was higher in TNBC tumour cells than in normal cells, suggesting activation due to accumulation of mutations, particularly in cancers with a high burden of structural mutations. SSA TNBC cell lines were also more sensitive to the drug Pevonedistat. Transcriptomic analyses revealed that in the drug-exposed condition, DNA damage repair and helicase-related pathways were significantly downregulated, in several of which BLM is a significant core gene. Our findings support incorporating ancestry into oncobiology in vitro modelling and conducting further studies to assess Pevonedistat as a potential TNBC treatment.",
  "abstract_shown": true,
  "affiliations": [
    "i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal",
    "IPATIMUP—Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal",
    "ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal",
    "Research Center of IPO-Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center (P.CCC) Raquel Seruca, 4200-162 Porto, Portugal",
    "FP-I3ID—Instituto de Investigação, Inovação e Desenvolvimento da Fundação Fernando Pessoa , University Fernando Pessoa, 4200-253 Porto, Portugal",
    "Department of Surgical Oncology, Portuguese Oncology Institute of Porto, 4200-162 Porto, Portugal",
    "School of Medicine and Biomedical Sciences, University Fernando Pessoa, 4420-096 Gondomar, Portugal",
    "Instituto Superior Técnico (IST), Universidade de Lisboa, 1049-001 Lisboa, Portugal",
    "Instituto de Engenharia de Sistemas e Computadores—Investigação e Desenvolvimento (INESC-ID), 1000-029 Lisboa, Portugal"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ricardo J. Pinto",
      "orcid": "0000-0002-4989-5138"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ana C. Magalhães",
      "orcid": "0000-0002-3988-3280"
    },
    {
      "affs": [
        0
      ],
      "name": "Clara M. Bento",
      "orcid": "0000-0001-9019-7334"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Fernanda Rosário",
      "orcid": "0000-0002-1269-8915"
    },
    {
      "affs": [
        3,
        4,
        5,
        6
      ],
      "name": "Lúcio Lara Santos",
      "orcid": "0000-0002-0521-5655"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Emanuel Gonçalves",
      "orcid": "0000-0002-9967-5205"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Luisa Pereira",
      "orcid": "0000-0002-4271-1527"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1wr2v7xr3dp81.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219980",
  "fulltext_url": null,
  "id": "1wr2v7xr3dp81",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9980",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-07",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/1wr2v7xr3dp81.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:21:27Z",
      "native_id": "10.3390/ijms27219980",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9980"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "In Vitro Models of Triple-Negative Breast Cancer of Sub-Saharan African Ancestry Suggest BLM-Centred DNA Damage Repair Dependency and Pevonedistat Sensitivity",
  "title_text": "In Vitro Models of Triple-Negative Breast Cancer of Sub-Saharan African Ancestry Suggest BLM-Centred DNA Damage Repair Dependency and Pevonedistat Sensitivity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:27Z",
  "url": "https://research.draconitic.com/paper/1wr2v7xr3dp81",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}