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<p>Next-generation sequencing (NGS) is essential for hereditary cancer diagnostics, as it detects single-nucleotide variants (SNVs), INDELs, and structural variants (SVs). Following ASCO recommendations for comprehensive sequence and structural analysis, we retrospectively analyzed a 25-gene NGS panel from 5,000 unrelated individuals, with or without personal history of cancer, to characterize the germline mutational spectrum associated with hereditary breast and ovarian cancer (HBOC). Among the participants, 12.7% carried pathogenic or likely pathogenic (P/LP) variants, predominantly comprising SNVs. A positive result was identified in 14% of individuals with a cancer diagnosis and in 7.5% of unaffected individuals. Most P/LP SNVs were identified in <i>BRCA1</i>/<i>2</i>, <i>CHEK2</i>, <i>TP53</i>, <i>ATM</i>, and <i>PALB2</i>. Structural variants accounted for 7.6% of all P/LP findings and were predominantly identified in <i>BRCA1/2</i> and <i>ATM</i>. Detection rates varied across tumor types, with more precise estimates observed in larger subgroups such as breast and ovarian cancer. Estimates derived from less frequent tumor types were associated with greater uncertainty due to smaller sample sizes. Variants of uncertain significance were identified in 25% of tests. This largest Brazilian HBOC cohort to date highlights that multigene panels identify P/LP variants even in unaffected individuals. These findings highlight the importance of incorporating SV detection into routine testing strategies and support efforts to expand access to genetic testing and counselling in Brazil.</p>

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Understanding the landscape of hereditary breast and ovarian cancer testing in Brazil

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月8日

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  • Daniele Paixão,
  • Anneliese Lopes Barth,
  • Andrea Kiss,
  • Vanessa Figueiredo Monteleone,
  • Betania Loures,
  • Juliana Emilia Prior Carnavalli,
  • Agatha Ribeiro Mendes,
  • Suzane De Andrade Barboza,
  • Bianca Mendes Souza,
  • Carolina Dias Carlos,
  • Lais Rodrigues Moura,
  • Mariana Rezende Bandeira de Mello,
  • Patricia Gonçalves Pereira Couto,
  • Amanda Thamires Batista Do Nascimento,
  • Caroline Mônaco Moreira,
  • Elisa Napolitano e Ferreira,
  • Wagner Antônio da Rosa Baratela,
  • Thálitta Hetamaro Ayala Lima

摘要

Next-generation sequencing (NGS) is essential for hereditary cancer diagnostics, as it detects single-nucleotide variants (SNVs), INDELs, and structural variants (SVs). Following ASCO recommendations for comprehensive sequence and structural analysis, we retrospectively analyzed a 25-gene NGS panel from 5,000 unrelated individuals, with or without personal history of cancer, to characterize the germline mutational spectrum associated with hereditary breast and ovarian cancer (HBOC). Among the participants, 12.7% carried pathogenic or likely pathogenic (P/LP) variants, predominantly comprising SNVs. A positive result was identified in 14% of individuals with a cancer diagnosis and in 7.5% of unaffected individuals. Most P/LP SNVs were identified in BRCA1/2, CHEK2, TP53, ATM, and PALB2. Structural variants accounted for 7.6% of all P/LP findings and were predominantly identified in BRCA1/2 and ATM. Detection rates varied across tumor types, with more precise estimates observed in larger subgroups such as breast and ovarian cancer. Estimates derived from less frequent tumor types were associated with greater uncertainty due to smaller sample sizes. Variants of uncertain significance were identified in 25% of tests. This largest Brazilian HBOC cohort to date highlights that multigene panels identify P/LP variants even in unaffected individuals. These findings highlight the importance of incorporating SV detection into routine testing strategies and support efforts to expand access to genetic testing and counselling in Brazil.