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Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis

Circulating tumor DNA (ctDNA) has emerged as a non-invasive “liquid biopsy” for early breast cancer diagnosis. We evaluated the suitability of ctDNA analysis in the diagnosis of early breast cancer after mammography findings, comparing PIK3CA and TP53 mutations between tumor biopsies and pre-biopsy...

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Autores principales: Jimenez Rodriguez, Begona, Diaz Córdoba, Gema, Garrido Aranda, Alicia, Álvarez, Martina, Vicioso, Luis, Llácer Pérez, Casilda, Hernando, Cristina, Bermejo, Begoña, Julve Parreño, Ana, Lluch, Ana, Ryder, Matthew B., Jones, Frederick S., Fredebohm, Johannes, Holtrup, Frank, Queipo-Ortuño, María Isabel, Alba, Emilio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723048/
https://www.ncbi.nlm.nih.gov/pubmed/31394872
http://dx.doi.org/10.3390/jcm8081183
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author Jimenez Rodriguez, Begona
Diaz Córdoba, Gema
Garrido Aranda, Alicia
Álvarez, Martina
Vicioso, Luis
Llácer Pérez, Casilda
Hernando, Cristina
Bermejo, Begoña
Julve Parreño, Ana
Lluch, Ana
Ryder, Matthew B.
Jones, Frederick S.
Fredebohm, Johannes
Holtrup, Frank
Queipo-Ortuño, María Isabel
Alba, Emilio
author_facet Jimenez Rodriguez, Begona
Diaz Córdoba, Gema
Garrido Aranda, Alicia
Álvarez, Martina
Vicioso, Luis
Llácer Pérez, Casilda
Hernando, Cristina
Bermejo, Begoña
Julve Parreño, Ana
Lluch, Ana
Ryder, Matthew B.
Jones, Frederick S.
Fredebohm, Johannes
Holtrup, Frank
Queipo-Ortuño, María Isabel
Alba, Emilio
author_sort Jimenez Rodriguez, Begona
collection PubMed
description Circulating tumor DNA (ctDNA) has emerged as a non-invasive “liquid biopsy” for early breast cancer diagnosis. We evaluated the suitability of ctDNA analysis in the diagnosis of early breast cancer after mammography findings, comparing PIK3CA and TP53 mutations between tumor biopsies and pre-biopsy circulating DNA. Matched plasma and frozen fresh tissue biopsies from patients with Breast Imaging-Reporting and Data System (BIRADS) 4c/5 mammography findings and subsequent diagnosis of primary breast cancer were analyzed using NGS TruSeq Custom Amplicon Low Input Panel (Illumina) and plasma SafeSEQ (Sysmex Inostics). The same plasma and tumor mutations were observed in eight of 29 patients (27.6%) with four in TP53 and five in PIK3CA mutations. Sequencing analysis also revealed four additional ctDNA mutations (three in TP53 and one in PIK3CA) previously not identified in three patients tissue biopsy. One of these patients had mutations in both genes. Age, tumor grade and size, immunohistochemical (IHC) subtype, BIRADS category, and lymph node positivity were significantly associated with the detectability of these blood tumor-derived mutations. In conclusion, ctDNA analysis could be used in early breast cancer diagnosis, providing critical clinical information to improve patient diagnosis.
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spelling pubmed-67230482019-09-10 Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis Jimenez Rodriguez, Begona Diaz Córdoba, Gema Garrido Aranda, Alicia Álvarez, Martina Vicioso, Luis Llácer Pérez, Casilda Hernando, Cristina Bermejo, Begoña Julve Parreño, Ana Lluch, Ana Ryder, Matthew B. Jones, Frederick S. Fredebohm, Johannes Holtrup, Frank Queipo-Ortuño, María Isabel Alba, Emilio J Clin Med Article Circulating tumor DNA (ctDNA) has emerged as a non-invasive “liquid biopsy” for early breast cancer diagnosis. We evaluated the suitability of ctDNA analysis in the diagnosis of early breast cancer after mammography findings, comparing PIK3CA and TP53 mutations between tumor biopsies and pre-biopsy circulating DNA. Matched plasma and frozen fresh tissue biopsies from patients with Breast Imaging-Reporting and Data System (BIRADS) 4c/5 mammography findings and subsequent diagnosis of primary breast cancer were analyzed using NGS TruSeq Custom Amplicon Low Input Panel (Illumina) and plasma SafeSEQ (Sysmex Inostics). The same plasma and tumor mutations were observed in eight of 29 patients (27.6%) with four in TP53 and five in PIK3CA mutations. Sequencing analysis also revealed four additional ctDNA mutations (three in TP53 and one in PIK3CA) previously not identified in three patients tissue biopsy. One of these patients had mutations in both genes. Age, tumor grade and size, immunohistochemical (IHC) subtype, BIRADS category, and lymph node positivity were significantly associated with the detectability of these blood tumor-derived mutations. In conclusion, ctDNA analysis could be used in early breast cancer diagnosis, providing critical clinical information to improve patient diagnosis. MDPI 2019-08-07 /pmc/articles/PMC6723048/ /pubmed/31394872 http://dx.doi.org/10.3390/jcm8081183 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jimenez Rodriguez, Begona
Diaz Córdoba, Gema
Garrido Aranda, Alicia
Álvarez, Martina
Vicioso, Luis
Llácer Pérez, Casilda
Hernando, Cristina
Bermejo, Begoña
Julve Parreño, Ana
Lluch, Ana
Ryder, Matthew B.
Jones, Frederick S.
Fredebohm, Johannes
Holtrup, Frank
Queipo-Ortuño, María Isabel
Alba, Emilio
Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis
title Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis
title_full Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis
title_fullStr Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis
title_full_unstemmed Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis
title_short Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis
title_sort detection of tp53 and pik3ca mutations in circulating tumor dna using next-generation sequencing in the screening process for early breast cancer diagnosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723048/
https://www.ncbi.nlm.nih.gov/pubmed/31394872
http://dx.doi.org/10.3390/jcm8081183
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