Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis

Autores organización

• Carlos Andres Castro Rojas

  Autor

• 

  Sandra Janneth Perdomo Lara

  Autor

Autores

• Ambriz-Barrera F.
• Rojas-Jiménez E.
• Díaz-Velásquez C.E.
• De-La-Cruz-Montoya A.H.
• Martínez-Gregorio H.
• Ruiz-De-La-Cruz M.
• Huertas A.
• Montealegre A.L.
• Acosta G.
• Vaca-Paniagua F.

Unidades de investigación

• Grupo de Inmunología celular y molecular Universidad El Bosque (InmuBo)

  Investigador

  Maria Consuelo Romero Sanchez

• Nutrición, Genética y Metabolismo

  Investigador

  Carlos Andres Castro Rojas

• Unidad de Epidemiología Clínica Oral UNIECLO

  Investigador

  Maria Rosa Buenahora Tobar

Resumen

Breast cancer (BC) has different molecular subgroups related to different risks and treatments. Tumor biopsies for BC detection are invasive and may not reflect tumor heterogeneity. Liquid biopsies have become relevant because they might overcome these limitations. We rationalize that liquid cfDNA biopsies through shallow whole genome sequencing (sWGS) could improve the detection of tumor alterations, complementing the genomic profiling. We evaluated the feasibility to detect somatic copy number alterations (SCNAs) in BC using shallow whole genome sequencing (sWGS) in cfDNA from archived samples from National Cancer Institute of Colombia patients. We sequenced tumor tissues from 38 BC patients with different molecular subtypes using a gene panel of 176 genes significantly mutated in cancer, and by liquid biopsies using sWGS on 20 paired samples to detect SCNAs and compare with the tumor samples. We identified an extensive intertumoral heterogeneity between the molecular subtypes of BC, with a mean tumor load of 602 mutations in the gene panel of tumor tissues. There was a 12.3% of concordance in deletions in the cfDNA-tumor pairs considering only the genes covered by the panel encompassing seven genes: BRCA1, CDK12, NF1, MAP2K4, NCOR1, TP53, and KEAP1 in three patients. This study shows the feasibility to complement the genomic analysis of tumor tissue biopsies to detect SCNA in BC using sWGS in cfDNA, providing a wider identification of potential therapeutic targets. Copyright: © 2024 Ambriz-Barrera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

• Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Cell-Free Nucleic Acids; Circulating Tumor DNA; DNA Copy Number Variations; Female; Humans; Middle Aged; Mutation; Whole Genome Sequencing; circulating free DNA; epidermal growth factor receptor 2; exoribonuclease; kelch like ECH associated protein 1; protein p53; cell free nucleic acid; circulating tumor DNA; tumor marker; adult; Akt signaling; Article; breast cancer; cancer staging; cancer tissue; cdk12 gene; cell adhesion; cell cycle regulation; clinical article; copy number variation; DNA extraction; DNA repair; female; gene; gene mutation; gene sequence; hematopoiesis; histology; human; human tissue; immunohistochemistry; invasive ductal carcinoma; male; map2k4 gene; MAPK signaling; middle aged; ncor1 gene; nf1 gene; Notch signaling; oxidative stress; paired end sequencing; pik3ca gene; RNA splicing; single nucleotide polymorphism; somatic copy number alteration; somatic mutation; spectrophotometry; treatment response; tumor gene;