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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.909615/full |
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| author | Mark A. Catherwood Dorte Wren Laura Chiecchio Doriane Cavalieri David Donaldson Sarah Lawless Ezzat ElHassadi Amjad Hayat Mary R. Cahill Derville O’Shea Jeremy Sargent Peter Stewart Manisha Maurya John Quinn Philip Murphy David Gonzalez de Castro Ken Mills Nicholas C. P. Cross Nicholas C. P. Cross Francesco Forconi Sunil Iyengar Anna Schuh Patrick Thornton |
| author_facet | Mark A. Catherwood Dorte Wren Laura Chiecchio Doriane Cavalieri David Donaldson Sarah Lawless Ezzat ElHassadi Amjad Hayat Mary R. Cahill Derville O’Shea Jeremy Sargent Peter Stewart Manisha Maurya John Quinn Philip Murphy David Gonzalez de Castro Ken Mills Nicholas C. P. Cross Nicholas C. P. Cross Francesco Forconi Sunil Iyengar Anna Schuh Patrick Thornton |
| author_sort | Mark A. Catherwood |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T12:29:22Z |
| format | Article |
| id | doaj.art-f68447793d1e43bead15fecab502e322 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T12:29:22Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f68447793d1e43bead15fecab502e3222022-12-22T03:33:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.909615909615TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre StudyMark A. Catherwood0Dorte Wren1Laura Chiecchio2Doriane Cavalieri3David Donaldson4Sarah Lawless5Ezzat ElHassadi6Amjad Hayat7Mary R. Cahill8Derville O’Shea9Jeremy Sargent10Peter Stewart11Manisha Maurya12John Quinn13Philip Murphy14David Gonzalez de Castro15Ken Mills16Nicholas C. P. Cross17Nicholas C. P. Cross18Francesco Forconi19Sunil Iyengar20Anna Schuh21Patrick Thornton22Haematology Department, Belfast Health and Social Care Trust, Belfast, United KingdomThe Royal Marsden Hospital and the Institute of Cancer Research, Biomedical Research Centre, London, United KingdomWessex Regional Genetics Laboratory, Salisbury National Health Service (NHS) Foundation Trust, Salisbury, United KingdomOxford Molecular Diagnostics Centre, Oxford University Hospitals, Oxford, United KingdomHaematology Department, Belfast Health and Social Care Trust, Belfast, United KingdomHaematology Department, Belfast Health and Social Care Trust, Belfast, United KingdomDepartment of Haematology, University Hospital Waterford, Waterford, IrelandDepartment of Haematology, University Hospital Galway, Galway, IrelandDepartment of Haematology, Cork University Hospital, Cork, IrelandDepartment of Haematology, Cork University Hospital, Cork, IrelandDepartment of Haematology, Our Lady of Lourdes Hospital, Queens University Belfast, Drogheda, IrelandCentre for Cancer Research and Cell Biology (CCRCB), Queen’s University Belfast, Belfast, United KingdomCentre for Cancer Research and Cell Biology (CCRCB), Queen’s University Belfast, Belfast, United Kingdom0Department of Haematology, Beaumont Hospital, Dublin, Ireland0Department of Haematology, Beaumont Hospital, Dublin, IrelandCentre for Cancer Research and Cell Biology (CCRCB), Queen’s University Belfast, Belfast, United KingdomCentre for Cancer Research and Cell Biology (CCRCB), Queen’s University Belfast, Belfast, United KingdomWessex Regional Genetics Laboratory, Salisbury National Health Service (NHS) Foundation Trust, Salisbury, United Kingdom1Faculty of Medicine, University of Southampton, Southampton, United Kingdom1Faculty of Medicine, University of Southampton, Southampton, United KingdomThe Royal Marsden Hospital and the Institute of Cancer Research, Biomedical Research Centre, London, United KingdomOxford Molecular Diagnostics Centre, Oxford University Hospitals, Oxford, United Kingdom0Department of Haematology, Beaumont Hospital, Dublin, IrelandLimited 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.909615/fullchronic lymphocytic leukaemiap53deletion 17pprognosisnext generation sequencing |
| spellingShingle | Mark A. Catherwood Dorte Wren Laura Chiecchio Doriane Cavalieri David Donaldson Sarah Lawless Ezzat ElHassadi Amjad Hayat Mary R. Cahill Derville O’Shea Jeremy Sargent Peter Stewart Manisha Maurya John Quinn Philip Murphy David Gonzalez de Castro Ken Mills Nicholas C. P. Cross Nicholas C. P. Cross Francesco Forconi Sunil Iyengar Anna Schuh Patrick Thornton TP53 Mutations Identified Using NGS Comprise the Overwhelming Majority of TP53 Disruptions in CLL: Results From a Multicentre Study Frontiers in Oncology chronic lymphocytic leukaemia p53 deletion 17p prognosis next generation sequencing |
| 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 | chronic lymphocytic leukaemia p53 deletion 17p prognosis next generation sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.909615/full |
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