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Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan‐cancer cohort

Tumour‐derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell‐free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we inte...

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Autores principales: Xu, Enwu, Su, Kai, Zhou, Yang, Gong, Longlong, Xuan, Yiwen, Liao, Ming, Cao, Jiawang, Li, Yaqian, Lu, Yujiao, Zhao, Yi, Chen, Fengxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572768/
https://www.ncbi.nlm.nih.gov/pubmed/34658138
http://dx.doi.org/10.1111/jcmm.16966
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author Xu, Enwu
Su, Kai
Zhou, Yang
Gong, Longlong
Xuan, Yiwen
Liao, Ming
Cao, Jiawang
Li, Yaqian
Lu, Yujiao
Zhao, Yi
Chen, Fengxia
author_facet Xu, Enwu
Su, Kai
Zhou, Yang
Gong, Longlong
Xuan, Yiwen
Liao, Ming
Cao, Jiawang
Li, Yaqian
Lu, Yujiao
Zhao, Yi
Chen, Fengxia
author_sort Xu, Enwu
collection PubMed
description Tumour‐derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell‐free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we integrated landscape of CH mutations in 11,725 pan‐cancer patients of Chinese and explored effects of CH on liquid biopsies in real‐world. We first identified 5933 CHs based on panel sequencing of matched DNA of white blood cell and cfDNA on 301 genes for 5100 patients, in which CH number of patients had positive correlation with their diagnosis age. We observed that canonical genes related to CH, including DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2 and SF3B1, were dominant in the Chinese cohort and 13.29% of CH mutations only appeared in the Chinese cohort compared with the Western cohort. Analysis of CH gene distribution bias indicated that CH tended to appear in genes with functions of tyrosine kinase regulation, PI3K‐Akt signalling and TP53 activity, suggesting unfavourable effects of CH mutations in cancer patients. We further confirmed effect of driver genes carried by CH on somatic mutations in liquid biopsy of cancer patients. Forty‐eight actionable somatic mutations in 17 driver genes were considered CH genes in 92 patients (1.80%) of the Chinese cohort, implying potential impacts of CH on clinical decision‐making. Taken together, this study exhibits strong evidence that gene mutations from CH interfere accuracy of liquid biopsies using cfDNA in cancer diagnosis and treatment in real‐world.
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spelling pubmed-85727682021-11-10 Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan‐cancer cohort Xu, Enwu Su, Kai Zhou, Yang Gong, Longlong Xuan, Yiwen Liao, Ming Cao, Jiawang Li, Yaqian Lu, Yujiao Zhao, Yi Chen, Fengxia J Cell Mol Med Original Articles Tumour‐derived DNA found in the plasma of cancer patients provides the probability to detect somatic mutations from circulating cell‐free DNA (cfDNA) in plasma samples. However, clonal hematopoiesis (CH) mutations affect the accuracy of liquid biopsy for cancer diagnosis and treatment. Here, we integrated landscape of CH mutations in 11,725 pan‐cancer patients of Chinese and explored effects of CH on liquid biopsies in real‐world. We first identified 5933 CHs based on panel sequencing of matched DNA of white blood cell and cfDNA on 301 genes for 5100 patients, in which CH number of patients had positive correlation with their diagnosis age. We observed that canonical genes related to CH, including DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2 and SF3B1, were dominant in the Chinese cohort and 13.29% of CH mutations only appeared in the Chinese cohort compared with the Western cohort. Analysis of CH gene distribution bias indicated that CH tended to appear in genes with functions of tyrosine kinase regulation, PI3K‐Akt signalling and TP53 activity, suggesting unfavourable effects of CH mutations in cancer patients. We further confirmed effect of driver genes carried by CH on somatic mutations in liquid biopsy of cancer patients. Forty‐eight actionable somatic mutations in 17 driver genes were considered CH genes in 92 patients (1.80%) of the Chinese cohort, implying potential impacts of CH on clinical decision‐making. Taken together, this study exhibits strong evidence that gene mutations from CH interfere accuracy of liquid biopsies using cfDNA in cancer diagnosis and treatment in real‐world. John Wiley and Sons Inc. 2021-10-17 2021-11 /pmc/articles/PMC8572768/ /pubmed/34658138 http://dx.doi.org/10.1111/jcmm.16966 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Xu, Enwu
Su, Kai
Zhou, Yang
Gong, Longlong
Xuan, Yiwen
Liao, Ming
Cao, Jiawang
Li, Yaqian
Lu, Yujiao
Zhao, Yi
Chen, Fengxia
Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan‐cancer cohort
title Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan‐cancer cohort
title_full Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan‐cancer cohort
title_fullStr Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan‐cancer cohort
title_full_unstemmed Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan‐cancer cohort
title_short Comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: A Chinese pan‐cancer cohort
title_sort comprehensive landscape and interference of clonal haematopoiesis mutations for liquid biopsy: a chinese pan‐cancer cohort
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572768/
https://www.ncbi.nlm.nih.gov/pubmed/34658138
http://dx.doi.org/10.1111/jcmm.16966
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