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Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach

Neoplastic cellularity contributes to the analytic sensitivity of most present technologies for mutation detection, such that they underperform when stroma and inflammatory cells dilute a cancer specimen’s variant fraction. Thus, tumor purity assessment by light microscopy is used to determine sampl...

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Autores principales: Patel, Nirali M., Jo, Heejoon, Eberhard, David A., Yin, Xiaoying, Hayward, Michele C., Stein, Matthew K., Hayes, David Neil, Grilley-Olson, Juneko E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887630/
https://www.ncbi.nlm.nih.gov/pubmed/30102605
http://dx.doi.org/10.1097/PAI.0000000000000684
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author Patel, Nirali M.
Jo, Heejoon
Eberhard, David A.
Yin, Xiaoying
Hayward, Michele C.
Stein, Matthew K.
Hayes, David Neil
Grilley-Olson, Juneko E.
author_facet Patel, Nirali M.
Jo, Heejoon
Eberhard, David A.
Yin, Xiaoying
Hayward, Michele C.
Stein, Matthew K.
Hayes, David Neil
Grilley-Olson, Juneko E.
author_sort Patel, Nirali M.
collection PubMed
description Neoplastic cellularity contributes to the analytic sensitivity of most present technologies for mutation detection, such that they underperform when stroma and inflammatory cells dilute a cancer specimen’s variant fraction. Thus, tumor purity assessment by light microscopy is used to determine sample adequacy before sequencing and to interpret the significance of negative results and mutant allele fraction afterwards. However, pathologist estimates of tumor purity are imprecise and have limited reproducibility. With the advent of massively parallel sequencing, large amounts of molecular data can be analyzed by computational purity algorithms. We retrospectively compared tumor purity of 3 computational algorithms with neoplastic cellularity using hematoxylin and eosin light microscopy to determine which was best for clinical evaluation of molecular profiling. Data were analyzed from 881 cancer patients from a clinical trial cohort, LCCC1108 (UNCseq), whose tumors had targeted massively parallel sequencing. Concordance among algorithms was poor, and the specimens analyzed had high rates of algorithm failure partially due to variable tumor purity. Computational tumor purity estimates did not add value beyond the pathologist’s estimate of neoplastic cellularity microscopy. To improve present methods, we propose a semiquantitative, clinically applicable strategy based on mutant allele fraction and copy number changes present within a given specimen, which when combined with the morphologic tumor purity estimate, guide the interpretation of next-generation sequencing results in cancer patients.
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spelling pubmed-68876302020-01-22 Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach Patel, Nirali M. Jo, Heejoon Eberhard, David A. Yin, Xiaoying Hayward, Michele C. Stein, Matthew K. Hayes, David Neil Grilley-Olson, Juneko E. Appl Immunohistochem Mol Morphol Research Articles Neoplastic cellularity contributes to the analytic sensitivity of most present technologies for mutation detection, such that they underperform when stroma and inflammatory cells dilute a cancer specimen’s variant fraction. Thus, tumor purity assessment by light microscopy is used to determine sample adequacy before sequencing and to interpret the significance of negative results and mutant allele fraction afterwards. However, pathologist estimates of tumor purity are imprecise and have limited reproducibility. With the advent of massively parallel sequencing, large amounts of molecular data can be analyzed by computational purity algorithms. We retrospectively compared tumor purity of 3 computational algorithms with neoplastic cellularity using hematoxylin and eosin light microscopy to determine which was best for clinical evaluation of molecular profiling. Data were analyzed from 881 cancer patients from a clinical trial cohort, LCCC1108 (UNCseq), whose tumors had targeted massively parallel sequencing. Concordance among algorithms was poor, and the specimens analyzed had high rates of algorithm failure partially due to variable tumor purity. Computational tumor purity estimates did not add value beyond the pathologist’s estimate of neoplastic cellularity microscopy. To improve present methods, we propose a semiquantitative, clinically applicable strategy based on mutant allele fraction and copy number changes present within a given specimen, which when combined with the morphologic tumor purity estimate, guide the interpretation of next-generation sequencing results in cancer patients. Lippincott Williams & Wilkins 2019 2018-08-10 /pmc/articles/PMC6887630/ /pubmed/30102605 http://dx.doi.org/10.1097/PAI.0000000000000684 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Research Articles
Patel, Nirali M.
Jo, Heejoon
Eberhard, David A.
Yin, Xiaoying
Hayward, Michele C.
Stein, Matthew K.
Hayes, David Neil
Grilley-Olson, Juneko E.
Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach
title Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach
title_full Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach
title_fullStr Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach
title_full_unstemmed Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach
title_short Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach
title_sort improved tumor purity metrics in next-generation sequencing for clinical practice: the integrated interpretation of neoplastic cellularity and sequencing results (iincase) approach
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887630/
https://www.ncbi.nlm.nih.gov/pubmed/30102605
http://dx.doi.org/10.1097/PAI.0000000000000684
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