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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783566740773404672 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7402350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kaurpushpinder apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT campodaniel apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT porrastaniab apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT ringalexander apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT lujanice apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT chairezyvonne apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT suyunyun apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT kangirene apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT langjuliee apilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT kaurpushpinder pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT campodaniel pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT porrastaniab pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT ringalexander pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT lujanice pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT chairezyvonne pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT suyunyun pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT kangirene pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer AT langjuliee pilotstudyforthefeasibilityofexomesequencingincirculatingtumorcellsversussinglemetastaticbiopsiesinbreastcancer |