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TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study
Limited data exists to show the correlation of (tumour protein 53) TP53 mutation detected by Next generation sequencing (NGS) and the presence/absence of deletions of 17p13 detected by FISH. The study which is the largest series to date includes 2332 CLL patients referred for analysis of del(17p) by...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273895/ https://www.ncbi.nlm.nih.gov/pubmed/35837095 http://dx.doi.org/10.3389/fonc.2022.909615 |
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author | Catherwood, Mark A. Wren, Dorte Chiecchio, Laura Cavalieri, Doriane Donaldson, David Lawless, Sarah ElHassadi, Ezzat Hayat, Amjad Cahill, Mary R. O’Shea, Derville Sargent, Jeremy Stewart, Peter Maurya, Manisha Quinn, John Murphy, Philip de Castro, David Gonzalez Mills, Ken Cross, Nicholas C. P. Forconi, Francesco Iyengar, Sunil Schuh, Anna Thornton, Patrick |
author_facet | Catherwood, Mark A. Wren, Dorte Chiecchio, Laura Cavalieri, Doriane Donaldson, David Lawless, Sarah ElHassadi, Ezzat Hayat, Amjad Cahill, Mary R. O’Shea, Derville Sargent, Jeremy Stewart, Peter Maurya, Manisha Quinn, John Murphy, Philip de Castro, David Gonzalez Mills, Ken Cross, Nicholas C. P. Forconi, Francesco Iyengar, Sunil Schuh, Anna Thornton, Patrick |
author_sort | Catherwood, Mark A. |
collection | PubMed |
description | Limited data exists to show the correlation of (tumour protein 53) TP53 mutation detected by Next generation sequencing (NGS) and the presence/absence of deletions of 17p13 detected by FISH. The study which is the largest series to date includes 2332 CLL patients referred for analysis of del(17p) by FISH and TP53 mutations by NGS before treatment. Using a 10% variant allele frequency (VAF) threshold, cases were segregated into high burden mutations (≥10%) and low burden mutations (<10%). TP53 aberrations (17p [del(17p)] and/or TP53 mutation) were detected in 320/2332 patients (13.7%). Using NGS analysis, 429 TP53 mutations were identified in 303 patients (13%). Of these 238 (79%) and 65 (21%) were cases with high burden and low burden mutations respectively. In our cohort, 2012 cases did not demonstrate a TP53 aberration (86.3%). A total of 159 cases showed TP53 mutations in the absence of del(17p) (49/159 with low burden TP53 mutations) and 144 cases had both TP53 mutation and del(17p) (16/144 with low burden mutations). Only 17/2332 (0.7%) cases demonstrated del(17p) with no TP53 mutation. Validated NGS protocols should be used in clinical decision making to avoid missing low-burden TP53 mutations and can detect the vast majority of TP53 aberrations. |
format | Online Article Text |
id | pubmed-9273895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92738952022-07-13 TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study Catherwood, Mark A. Wren, Dorte Chiecchio, Laura Cavalieri, Doriane Donaldson, David Lawless, Sarah ElHassadi, Ezzat Hayat, Amjad Cahill, Mary R. O’Shea, Derville Sargent, Jeremy Stewart, Peter Maurya, Manisha Quinn, John Murphy, Philip de Castro, David Gonzalez Mills, Ken Cross, Nicholas C. P. Forconi, Francesco Iyengar, Sunil Schuh, Anna Thornton, Patrick Front Oncol Oncology Limited data exists to show the correlation of (tumour protein 53) TP53 mutation detected by Next generation sequencing (NGS) and the presence/absence of deletions of 17p13 detected by FISH. The study which is the largest series to date includes 2332 CLL patients referred for analysis of del(17p) by FISH and TP53 mutations by NGS before treatment. Using a 10% variant allele frequency (VAF) threshold, cases were segregated into high burden mutations (≥10%) and low burden mutations (<10%). TP53 aberrations (17p [del(17p)] and/or TP53 mutation) were detected in 320/2332 patients (13.7%). Using NGS analysis, 429 TP53 mutations were identified in 303 patients (13%). Of these 238 (79%) and 65 (21%) were cases with high burden and low burden mutations respectively. In our cohort, 2012 cases did not demonstrate a TP53 aberration (86.3%). A total of 159 cases showed TP53 mutations in the absence of del(17p) (49/159 with low burden TP53 mutations) and 144 cases had both TP53 mutation and del(17p) (16/144 with low burden mutations). Only 17/2332 (0.7%) cases demonstrated del(17p) with no TP53 mutation. Validated NGS protocols should be used in clinical decision making to avoid missing low-burden TP53 mutations and can detect the vast majority of TP53 aberrations. Frontiers Media S.A. 2022-06-28 /pmc/articles/PMC9273895/ /pubmed/35837095 http://dx.doi.org/10.3389/fonc.2022.909615 Text en Copyright © 2022 Catherwood, Wren, Chiecchio, Cavalieri, Donaldson, Lawless, ElHassadi, Hayat, Cahill, O’Shea, Sargent, Stewart, Maurya, Quinn, Murphy, de Castro, Mills, Cross, Forconi, Iyengar, Schuh and Thornton https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Catherwood, Mark A. Wren, Dorte Chiecchio, Laura Cavalieri, Doriane Donaldson, David Lawless, Sarah ElHassadi, Ezzat Hayat, Amjad Cahill, Mary R. O’Shea, Derville Sargent, Jeremy Stewart, Peter Maurya, Manisha Quinn, John Murphy, Philip de Castro, David Gonzalez Mills, Ken Cross, Nicholas C. P. Forconi, Francesco Iyengar, Sunil Schuh, Anna Thornton, Patrick TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study |
title |
TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study |
title_full |
TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study |
title_fullStr |
TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study |
title_full_unstemmed |
TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study |
title_short |
TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study |
title_sort | tp53 mutations identified using ngs comprise the overwhelming majority of tp53 disruptions in cll: results from a multicentre study |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273895/ https://www.ncbi.nlm.nih.gov/pubmed/35837095 http://dx.doi.org/10.3389/fonc.2022.909615 |
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