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Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications

The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH) in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA) are proposed as prognostic biomarkers to stratify...

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Autores principales: Cresswell, George D., Apps, John R., Chagtai, Tasnim, Mifsud, Borbala, Bentley, Christopher C., Maschietto, Mariana, Popov, Sergey D., Weeks, Mark E., Olsen, Øystein E., Sebire, Neil J., Pritchard-Jones, Kathy, Luscombe, Nicholas M., Williams, Richard D., Mifsud, William
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972528/
https://www.ncbi.nlm.nih.gov/pubmed/27333041
http://dx.doi.org/10.1016/j.ebiom.2016.05.029
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author Cresswell, George D.
Apps, John R.
Chagtai, Tasnim
Mifsud, Borbala
Bentley, Christopher C.
Maschietto, Mariana
Popov, Sergey D.
Weeks, Mark E.
Olsen, Øystein E.
Sebire, Neil J.
Pritchard-Jones, Kathy
Luscombe, Nicholas M.
Williams, Richard D.
Mifsud, William
author_facet Cresswell, George D.
Apps, John R.
Chagtai, Tasnim
Mifsud, Borbala
Bentley, Christopher C.
Maschietto, Mariana
Popov, Sergey D.
Weeks, Mark E.
Olsen, Øystein E.
Sebire, Neil J.
Pritchard-Jones, Kathy
Luscombe, Nicholas M.
Williams, Richard D.
Mifsud, William
author_sort Cresswell, George D.
collection PubMed
description The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH) in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA) are proposed as prognostic biomarkers to stratify patients, for example 1q + in Wilms tumor (WT); current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q + is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect > 95% of cases with 1q +. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution.
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spelling pubmed-49725282016-08-10 Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications Cresswell, George D. Apps, John R. Chagtai, Tasnim Mifsud, Borbala Bentley, Christopher C. Maschietto, Mariana Popov, Sergey D. Weeks, Mark E. Olsen, Øystein E. Sebire, Neil J. Pritchard-Jones, Kathy Luscombe, Nicholas M. Williams, Richard D. Mifsud, William EBioMedicine Research Paper The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH) in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA) are proposed as prognostic biomarkers to stratify patients, for example 1q + in Wilms tumor (WT); current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q + is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect > 95% of cases with 1q +. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution. Elsevier 2016-05-27 /pmc/articles/PMC4972528/ /pubmed/27333041 http://dx.doi.org/10.1016/j.ebiom.2016.05.029 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Cresswell, George D.
Apps, John R.
Chagtai, Tasnim
Mifsud, Borbala
Bentley, Christopher C.
Maschietto, Mariana
Popov, Sergey D.
Weeks, Mark E.
Olsen, Øystein E.
Sebire, Neil J.
Pritchard-Jones, Kathy
Luscombe, Nicholas M.
Williams, Richard D.
Mifsud, William
Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications
title Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications
title_full Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications
title_fullStr Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications
title_full_unstemmed Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications
title_short Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications
title_sort intra-tumor genetic heterogeneity in wilms tumor: clonal evolution and clinical implications
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972528/
https://www.ncbi.nlm.nih.gov/pubmed/27333041
http://dx.doi.org/10.1016/j.ebiom.2016.05.029
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