A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer

The comparison of the landscape of somatic alterations in circulating tumor cells (CTCs) versus metastases is challenging. Here, we comprehensively characterized the somatic landscape in bulk (amplified and non-amplified), spike-in breast cancer cells, CTCs, and metastases from breast cancer patient...

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Autores principales: Kaur, Pushpinder, Campo, Daniel, Porras, Tania B., Ring, Alexander, Lu, Janice, Chairez, Yvonne, Su, Yunyun, Kang, Irene, Lang, Julie E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402350/
https://www.ncbi.nlm.nih.gov/pubmed/32650480
http://dx.doi.org/10.3390/ijms21144826
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author Kaur, Pushpinder
Campo, Daniel
Porras, Tania B.
Ring, Alexander
Lu, Janice
Chairez, Yvonne
Su, Yunyun
Kang, Irene
Lang, Julie E.
author_facet Kaur, Pushpinder
Campo, Daniel
Porras, Tania B.
Ring, Alexander
Lu, Janice
Chairez, Yvonne
Su, Yunyun
Kang, Irene
Lang, Julie E.
author_sort Kaur, Pushpinder
collection PubMed
description The comparison of the landscape of somatic alterations in circulating tumor cells (CTCs) versus metastases is challenging. Here, we comprehensively characterized the somatic landscape in bulk (amplified and non-amplified), spike-in breast cancer cells, CTCs, and metastases from breast cancer patients using whole-exome sequencing (WES). We determined the level of genomic concordance for somatic nucleotide variants (SNVs), copy number alterations (CNAs), and structural variants (SVs). The variant allele fractions (VAFs) of somatic variants were remarkably similar between amplified and non-amplified cell line samples as technical replicates. In clinical samples, a significant fraction of somatic variants had low VAFs in CTCs compared to metastases. The most frequently recurrent gene mutations in clinical samples were associated with an elevated C > T mutational signature. We found complex rearrangement patterns including intra- and inter-chromosomal rearrangements, singleton, and recurrent gene fusions, and tandem duplications. We observed high molecular discordance for somatic alterations between paired samples consistent with marked heterogeneity of the somatic landscape. The most prevalent copy number calls were focal deletion events in CTCs and metastases. Our results demonstrate the feasibility of an integrated workflow for the identification of a complete repertoire of somatic alterations and highlight the intrapatient genomic differences that occur between CTCs and metastases.
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spelling pubmed-74023502020-08-18 A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer Kaur, Pushpinder Campo, Daniel Porras, Tania B. Ring, Alexander Lu, Janice Chairez, Yvonne Su, Yunyun Kang, Irene Lang, Julie E. Int J Mol Sci Article The comparison of the landscape of somatic alterations in circulating tumor cells (CTCs) versus metastases is challenging. Here, we comprehensively characterized the somatic landscape in bulk (amplified and non-amplified), spike-in breast cancer cells, CTCs, and metastases from breast cancer patients using whole-exome sequencing (WES). We determined the level of genomic concordance for somatic nucleotide variants (SNVs), copy number alterations (CNAs), and structural variants (SVs). The variant allele fractions (VAFs) of somatic variants were remarkably similar between amplified and non-amplified cell line samples as technical replicates. In clinical samples, a significant fraction of somatic variants had low VAFs in CTCs compared to metastases. The most frequently recurrent gene mutations in clinical samples were associated with an elevated C > T mutational signature. We found complex rearrangement patterns including intra- and inter-chromosomal rearrangements, singleton, and recurrent gene fusions, and tandem duplications. We observed high molecular discordance for somatic alterations between paired samples consistent with marked heterogeneity of the somatic landscape. The most prevalent copy number calls were focal deletion events in CTCs and metastases. Our results demonstrate the feasibility of an integrated workflow for the identification of a complete repertoire of somatic alterations and highlight the intrapatient genomic differences that occur between CTCs and metastases. MDPI 2020-07-08 /pmc/articles/PMC7402350/ /pubmed/32650480 http://dx.doi.org/10.3390/ijms21144826 Text en © 2020 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
Kaur, Pushpinder
Campo, Daniel
Porras, Tania B.
Ring, Alexander
Lu, Janice
Chairez, Yvonne
Su, Yunyun
Kang, Irene
Lang, Julie E.
A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer
title A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer
title_full A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer
title_fullStr A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer
title_full_unstemmed A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer
title_short A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer
title_sort pilot study for the feasibility of exome-sequencing in circulating tumor cells versus single metastatic biopsies in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402350/
https://www.ncbi.nlm.nih.gov/pubmed/32650480
http://dx.doi.org/10.3390/ijms21144826
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