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<p>The burden of triple-negative breast cancer (TNBC) may be shaped by genetic factors, particularly inherited and somatic mutation profiles. However, data on this topic remain limited, especially for the African continent, where a higher TNBC incidence is observed. In the age of precision medicine, cataloguing TNBC diversity in African patients becomes imperative. We performed whole exome sequencing, including untranslated regions, on 30 samples from Angola and Cape Verde, which allowed to ascertain on potential regulatory mutations in TNBC for the first time. A high somatic burden was observed for the African cohort, with 86% of variants being so far unreported. Recurring to predictive functional algorithms, 17% of the somatic single nucleotide variants were predicted to be deleterious at the protein level, and 20% overlapped with candidate cis-regulatory elements controlling gene expression. Several of these somatic functionally-impactful mutations and copy number variation (mainly in 1q, 8q, 6 and 10p) occur in known BC- and all cancer-driver genes, enriched for several cancer mechanisms, including response to radiation and related DNA repair mechanisms. <i>TP53</i> is the top of these known BC-driver genes, but our results identified possible novel TNBC driver genes that may play a main role in the African context, as <i>TTN</i>, <i>CEACAM7</i>, <i>DEFB132</i>, <i>COPZ2</i> and <i>GAS1</i>. These findings emphasize the need to expand cancer omics screenings across the African continent, the region of the globe with highest genomic diversity, accelerating the discovery of new somatic mutations and cancer-related pathways.</p>

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Coding and regulatory somatic profiling of triple-negative breast cancer in Sub-Saharan African patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月25日

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  • Ricardo J. Pinto,
  • Dylan Ferreira,
  • Paulo Salamanca,
  • Fernando Miguel,
  • Pamela Borges,
  • Carla Barbosa,
  • Vitor Costa,
  • Carlos Lopes,
  • Lúcio Lara Santos,
  • Luisa Pereira

摘要

The burden of triple-negative breast cancer (TNBC) may be shaped by genetic factors, particularly inherited and somatic mutation profiles. However, data on this topic remain limited, especially for the African continent, where a higher TNBC incidence is observed. In the age of precision medicine, cataloguing TNBC diversity in African patients becomes imperative. We performed whole exome sequencing, including untranslated regions, on 30 samples from Angola and Cape Verde, which allowed to ascertain on potential regulatory mutations in TNBC for the first time. A high somatic burden was observed for the African cohort, with 86% of variants being so far unreported. Recurring to predictive functional algorithms, 17% of the somatic single nucleotide variants were predicted to be deleterious at the protein level, and 20% overlapped with candidate cis-regulatory elements controlling gene expression. Several of these somatic functionally-impactful mutations and copy number variation (mainly in 1q, 8q, 6 and 10p) occur in known BC- and all cancer-driver genes, enriched for several cancer mechanisms, including response to radiation and related DNA repair mechanisms. TP53 is the top of these known BC-driver genes, but our results identified possible novel TNBC driver genes that may play a main role in the African context, as TTN, CEACAM7, DEFB132, COPZ2 and GAS1. These findings emphasize the need to expand cancer omics screenings across the African continent, the region of the globe with highest genomic diversity, accelerating the discovery of new somatic mutations and cancer-related pathways.