Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis.
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 b...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0308176 |
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| author | Fernando Ambriz-Barrera Ernesto Rojas-Jiménez Clara Estela Díaz-Velásquez Aldo Hugo De-La-Cruz-Montoya Héctor Martínez-Gregorio Miguel Ruiz-De-La-Cruz Antonio Huertas Ana Lorena Montealegre Carlos Castro-Rojas Gabriela Acosta Felipe Vaca-Paniagua Sandra Perdomo |
| author_facet | Fernando Ambriz-Barrera Ernesto Rojas-Jiménez Clara Estela Díaz-Velásquez Aldo Hugo De-La-Cruz-Montoya Héctor Martínez-Gregorio Miguel Ruiz-De-La-Cruz Antonio Huertas Ana Lorena Montealegre Carlos Castro-Rojas Gabriela Acosta Felipe Vaca-Paniagua Sandra Perdomo |
| author_sort | Fernando Ambriz-Barrera |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-53151c0a7a1c474c98a587b0169919bb |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-53151c0a7a1c474c98a587b0169919bb2025-08-20T03:46:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01199e030817610.1371/journal.pone.0308176Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis.Fernando Ambriz-BarreraErnesto Rojas-JiménezClara Estela Díaz-VelásquezAldo Hugo De-La-Cruz-MontoyaHéctor Martínez-GregorioMiguel Ruiz-De-La-CruzAntonio HuertasAna Lorena MontealegreCarlos Castro-RojasGabriela AcostaFelipe Vaca-PaniaguaSandra PerdomoBreast 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.https://doi.org/10.1371/journal.pone.0308176 |
| spellingShingle | Fernando Ambriz-Barrera Ernesto Rojas-Jiménez Clara Estela Díaz-Velásquez Aldo Hugo De-La-Cruz-Montoya Héctor Martínez-Gregorio Miguel Ruiz-De-La-Cruz Antonio Huertas Ana Lorena Montealegre Carlos Castro-Rojas Gabriela Acosta Felipe Vaca-Paniagua Sandra Perdomo Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis. PLoS ONE |
| title | Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis. |
| title_full | Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis. |
| title_fullStr | Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis. |
| title_full_unstemmed | Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis. |
| title_short | Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis. |
| title_sort | mutational spectrum of breast cancer by shallow whole genome sequencing of cfdna and tumor gene panel analysis |
| url | https://doi.org/10.1371/journal.pone.0308176 |
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