Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL
Abstract In chronic lymphocytic leukemia, the reliability of next‐generation sequencing (NGS) to detect TP53 variants ≤10% allelic frequency (low‐VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%...
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2025-01-01
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| author | Sarka Pavlova Jitka Malcikova Lenka Radova Silvia Bonfiglio Jack B. Cowland Christian Brieghel Mette K. Andersen Maria Karypidou Bella Biderman Michael Doubek Gregory Lazarian Inmaculada Rapado Matthijs Vynck Naomi A. Porret Martin Andres Dina Rosenberg Dvora Sahar Carolina Martínez‐Laperche Ismael Buño Andrew Hindley David Donaldson Julio B. Sánchez José A. García‐Marco Alicia Serrano‐Alcalá Blanca Ferrer‐Lores Concepción Fernández‐Rodriguez Beatriz Bellosillo Stephan Stilgenbauer Eugen Tausch Hero Nikdin Fiona Quinn Emer Atkinson Lisette van deCorput Cafer Yildiz Cristina Bilbao‐Sieyro Yanira Florido Christian Thiede Caroline Schuster Anastazja Stoj Sylwia Czekalska Anastasia Chatzidimitriou Stamatia Laidou Audrey Bidet Charles Dussiau Friedel Nollet Giovanna Piras Maria Monne Svetlana Smirnova Eugene Nikitin Ivan Sloma Alexis Claudel Laetitia Largeaud Loïc Ysebaert Peter J. M. Valk Amy Christian Renata Walewska David Oscier Marta Sebastião Maria Gomes daSilva Piero Galieni Mario Angelini Davide Rossi Valeria Spina Sónia Matos Vânia Martins Tomasz Stokłosa Monika Pepek Panagiotis Baliakas Rafa Andreu Irene Luna Tiina Kahre Ülle Murumets Tereza Pikousova Terezia Kurucova Sophie Laird Daniel Ward Miguel Alcoceba Ana Balanzategui Lydia Scarfo Francesca Gandini Ettore Zapparoli Adoración Blanco Pau Abrisqueta Ana E. Rodríguez‐Vicente Rocío Benito Clotilde Bravetti Frédéric Davi Paula Gameiro Joaquin Martinez‐Lopez Bárbara Tazón‐Vega Fanny Baran‐Marszak Zadie Davis Mark Catherwood Andrey Sudarikov Richard Rosenquist Carsten U. Niemann Kostas Stamatopoulos Paolo Ghia Sarka Pospisilova |
| author_facet | Sarka Pavlova Jitka Malcikova Lenka Radova Silvia Bonfiglio Jack B. Cowland Christian Brieghel Mette K. Andersen Maria Karypidou Bella Biderman Michael Doubek Gregory Lazarian Inmaculada Rapado Matthijs Vynck Naomi A. Porret Martin Andres Dina Rosenberg Dvora Sahar Carolina Martínez‐Laperche Ismael Buño Andrew Hindley David Donaldson Julio B. Sánchez José A. García‐Marco Alicia Serrano‐Alcalá Blanca Ferrer‐Lores Concepción Fernández‐Rodriguez Beatriz Bellosillo Stephan Stilgenbauer Eugen Tausch Hero Nikdin Fiona Quinn Emer Atkinson Lisette van deCorput Cafer Yildiz Cristina Bilbao‐Sieyro Yanira Florido Christian Thiede Caroline Schuster Anastazja Stoj Sylwia Czekalska Anastasia Chatzidimitriou Stamatia Laidou Audrey Bidet Charles Dussiau Friedel Nollet Giovanna Piras Maria Monne Svetlana Smirnova Eugene Nikitin Ivan Sloma Alexis Claudel Laetitia Largeaud Loïc Ysebaert Peter J. M. Valk Amy Christian Renata Walewska David Oscier Marta Sebastião Maria Gomes daSilva Piero Galieni Mario Angelini Davide Rossi Valeria Spina Sónia Matos Vânia Martins Tomasz Stokłosa Monika Pepek Panagiotis Baliakas Rafa Andreu Irene Luna Tiina Kahre Ülle Murumets Tereza Pikousova Terezia Kurucova Sophie Laird Daniel Ward Miguel Alcoceba Ana Balanzategui Lydia Scarfo Francesca Gandini Ettore Zapparoli Adoración Blanco Pau Abrisqueta Ana E. Rodríguez‐Vicente Rocío Benito Clotilde Bravetti Frédéric Davi Paula Gameiro Joaquin Martinez‐Lopez Bárbara Tazón‐Vega Fanny Baran‐Marszak Zadie Davis Mark Catherwood Andrey Sudarikov Richard Rosenquist Carsten U. Niemann Kostas Stamatopoulos Paolo Ghia Sarka Pospisilova |
| author_sort | Sarka Pavlova |
| collection | DOAJ |
| description | Abstract In chronic lymphocytic leukemia, the reliability of next‐generation sequencing (NGS) to detect TP53 variants ≤10% allelic frequency (low‐VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%, 94.5%, and 94.8% at 1%, 2%, and 3% VAF cut‐off, respectively. While only one false positive (FP) result was reported at >2% VAF, it was more challenging to distinguish true variants <2% VAF from background noise (37 FPs reported by 9 laboratories). The impact of low‐VAF variants on time‐to‐second‐treatment (TTST) and overall survival (OS) was investigated in a series of 1092 patients. Among patients not treated with targeted agents, patients with low‐VAF TP53 variants had shorter TTST and OS versus wt‐TP53 patients, and the relative risk of second‐line treatment or death increased continuously with increasing VAF. Targeted therapy in ≥2 line diminished the difference in OS between patients with low‐VAF TP53 variants and wt‐TP53 patients, while patients with high‐VAF TP53 variants had inferior OS compared to wild type‐TP53 cases. Altogether, NGS‐based approaches are technically capable of detecting low‐VAF variants. No strict threshold can be suggested from a technical standpoint, laboratories reporting TP53 mutations should participate in a standardized validation set‐up. Finally, whereas low‐VAF variants affected outcomes in patients receiving chemoimmunotherapy, their impact on those treated with novel therapies remains undetermined. Our results pave the way for the harmonized and accurate TP53 assessment, which is indispensable for elucidating the role of TP53 mutations in targeted treatment. |
| format | Article |
| id | doaj-art-92c47c3a602340e8a01b1b67106e6a6b |
| institution | OA Journals |
| issn | 2572-9241 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj-art-92c47c3a602340e8a01b1b67106e6a6b2025-08-20T02:11:46ZengWileyHemaSphere2572-92412025-01-0191n/an/a10.1002/hem3.70065Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLLSarka Pavlova0Jitka Malcikova1Lenka Radova2Silvia Bonfiglio3Jack B. Cowland4Christian Brieghel5Mette K. Andersen6Maria Karypidou7Bella Biderman8Michael Doubek9Gregory Lazarian10Inmaculada Rapado11Matthijs Vynck12Naomi A. Porret13Martin Andres14Dina Rosenberg15Dvora Sahar16Carolina Martínez‐Laperche17Ismael Buño18Andrew Hindley19David Donaldson20Julio B. Sánchez21José A. García‐Marco22Alicia Serrano‐Alcalá23Blanca Ferrer‐Lores24Concepción Fernández‐Rodriguez25Beatriz Bellosillo26Stephan Stilgenbauer27Eugen Tausch28Hero Nikdin29Fiona Quinn30Emer Atkinson31Lisette van deCorput32Cafer Yildiz33Cristina Bilbao‐Sieyro34Yanira Florido35Christian Thiede36Caroline Schuster37Anastazja Stoj38Sylwia Czekalska39Anastasia Chatzidimitriou40Stamatia Laidou41Audrey Bidet42Charles Dussiau43Friedel Nollet44Giovanna Piras45Maria Monne46Svetlana Smirnova47Eugene Nikitin48Ivan Sloma49Alexis Claudel50Laetitia Largeaud51Loïc Ysebaert52Peter J. M. Valk53Amy Christian54Renata Walewska55David Oscier56Marta Sebastião57Maria Gomes daSilva58Piero Galieni59Mario Angelini60Davide Rossi61Valeria Spina62Sónia Matos63Vânia Martins64Tomasz Stokłosa65Monika Pepek66Panagiotis Baliakas67Rafa Andreu68Irene Luna69Tiina Kahre70Ülle Murumets71Tereza Pikousova72Terezia Kurucova73Sophie Laird74Daniel Ward75Miguel Alcoceba76Ana Balanzategui77Lydia Scarfo78Francesca Gandini79Ettore Zapparoli80Adoración Blanco81Pau Abrisqueta82Ana E. Rodríguez‐Vicente83Rocío Benito84Clotilde Bravetti85Frédéric Davi86Paula Gameiro87Joaquin Martinez‐Lopez88Bárbara Tazón‐Vega89Fanny Baran‐Marszak90Zadie Davis91Mark Catherwood92Andrey Sudarikov93Richard Rosenquist94Carsten U. Niemann95Kostas Stamatopoulos96Paolo Ghia97Sarka Pospisilova98Department of Internal Medicine, Hematology and Oncology, and Institute of Medical Genetics and Genomics, University Hospital Brno and Medical Faculty Masaryk University Brno Czech RepublicDepartment of Internal Medicine, Hematology and Oncology, and Institute of Medical Genetics and Genomics, University Hospital Brno and Medical Faculty Masaryk University Brno Czech RepublicCentre for Molecular Medicine, Central European Institute of Technology (CEITEC) Masaryk University Brno Czech RepublicB‐Cell Neoplasia Unit and Strategic Research Program on CLL IRCCS Ospedale San Raffaele Milan ItalyDepartment of Clinical Genetics, Centre of Diagnostic Investigations Copenhagen University Hospital ‐ Rigshospitalet Copenhagen DenmarkDepartment of Hematology Copenhagen University Hospital ‐ Rigshospitalet Copenhagen DenmarkDepartment of Clinical Genetics, Centre of Diagnostic Investigations Copenhagen University Hospital ‐ Rigshospitalet Copenhagen DenmarkInstitute of Applied Biosciences Centre for Research and Technology Hellas Thessaloniki GreeceNational Medical Research Center for Hematology Moscow RussiaDepartment of Internal Medicine, Hematology and Oncology, and Institute of Medical Genetics and Genomics, University Hospital Brno and Medical Faculty Masaryk University Brno Czech RepublicHematology laboratory HUPSSD, Hôpital Avicenne, APHP Bobigny FranceDepartment of Hematology Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Complutense University, CNIO, CIBERONC Madrid SpainDepartment of Laboratory Medicine AZ Sint‐Jan Hospital Bruges BelgiumDepartment of Hematology and Central Hematology Laboratory, Inselspital Bern University Hospital, University of Bern Bern SwitzerlandDepartment of Hematology and Central Hematology Laboratory, Inselspital Bern University Hospital, University of Bern Bern SwitzerlandHematology Laboratory Rambam Medical Center Haifa IsraelHematology Laboratory Rambam Medical Center Haifa IsraelDepartment of Hematology Gregorio Marañón General University Hospital, Gregorio Marañón Health Research Institute (IiSGM) Madrid SpainDepartment of Hematology Gregorio Marañón General University Hospital, Gregorio Marañón Health Research Institute (IiSGM) Madrid SpainHaematology Department Belfast City Hospital Belfast UKHaematology Department Belfast City Hospital Belfast UKMolecular Cytogenetics Unit, Hematology Department Hospital Universitario Puerta de Hierro‐Majadahonda Madrid SpainMolecular Cytogenetics Unit, Hematology Department Hospital Universitario Puerta de Hierro‐Majadahonda Madrid SpainHematology Department Hospital Clínico Universitario‐INCLIVA Valencia SpainHematology Department Hospital Clínico Universitario‐INCLIVA Valencia SpainPathology Department Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute) Barcelona SpainPathology Department Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute) Barcelona SpainDepartment of Internal Medicine III Ulm University Ulm GermanyDepartment of Internal Medicine III Ulm University Ulm GermanyDepartment of Molecular Medicine and Surgery Karolinska Institutet Stockholm SwedenCancer Molecular Diagnostics Department Centre for Laboratory Medicine and Molecular Pathology, St. James Hospital Dublin IrelandCancer Molecular Diagnostics Department Centre for Laboratory Medicine and Molecular Pathology, St. James Hospital Dublin IrelandCentral Diagnostic Laboratory University Medical Center Utrecht Utrecht The NetherlandsCentral Diagnostic Laboratory University Medical Center Utrecht Utrecht The NetherlandsServicio de Hematología Hospital Universitario de Gran Canaria Dr. Negrín, Departamento de Morfología de La Universidad de Las Palmas de Gran Canaria Gran Canaria SpainServicio de Hematología Hospital Universitario de Gran Canaria Dr. Negrín, Departamento de Morfología de La Universidad de Las Palmas de Gran Canaria Gran Canaria SpainAgenDix GmbH Dresden GermanyAgenDix GmbH Dresden GermanyDepartment of Hematological Diagnostics and Genetics University Hospital in Krakow Krakow PolandDepartment of Hematological Diagnostics and Genetics University Hospital in Krakow Krakow PolandInstitute of Applied Biosciences Centre for Research and Technology Hellas Thessaloniki GreeceInstitute of Applied Biosciences Centre for Research and Technology Hellas Thessaloniki GreeceLaboratoire d'Hématologie Biologique CHU Bordeaux Bordeaux FranceLaboratoire d'Hématologie Biologique CHU Bordeaux Bordeaux FranceDepartment of Laboratory Medicine AZ Sint‐Jan Hospital Bruges BelgiumLaboratorio specialistico UOC ematologia Ospedale San Francesco ASL Nuoro ItalyLaboratorio specialistico UOC ematologia Ospedale San Francesco ASL Nuoro ItalyNational Medical Research Center for Hematology Moscow RussiaOutpatient department of Hematology, Oncology and Chemotherapy, Botkin Hospital, and Department of Hematology and Transfusiology Russian Medical Academy of Continuous Professional Education Moscow RussiaUniv Paris Est Creteil, INSERM, IMRB Creteil FranceUniv Paris Est Creteil, INSERM, IMRB Creteil FranceInstitut Universitaire de Cancérologie de Toulouse Toulouse FranceInstitut Universitaire de Cancérologie de Toulouse Toulouse FranceDepartment of Hematology, Erasmus MC Cancer Institute University Medical Center Rotterdam Rotterdam The NetherlandsMolecular Pathology University Hospitals Dorset Bournemouth UKMolecular Pathology University Hospitals Dorset Bournemouth UKMolecular Pathology University Hospitals Dorset Bournemouth UKLaboratório Hemato‐Oncologia Instituto Português de Oncologia de Lisboa Lisbon PortugalServiço de Hematologia Instituto Português de Oncologia de Lisboa Lisbon PortugalUOC Hematology Mazzoni Hospital‐Ascoli Piceno Ascoli Piceno ItalyUOC Hematology Mazzoni Hospital‐Ascoli Piceno Ascoli Piceno ItalyInstitute of Oncology Research and Oncology Institute of Southern Switzerland Bellinzona SwitzerlandLaboratorio di Diagnostica Molecolare, Servizio di Genetica Medica EOLAB Ente Ospedaliero Cantonale Bellinzona SwitzerlandGenomed‐Diagnósticos de Medicina Molecular iMM ‐ Instituto de Medicina Molecular, Faculdade de Medicina Lisboa PortugalGenomed‐Diagnósticos de Medicina Molecular iMM ‐ Instituto de Medicina Molecular, Faculdade de Medicina Lisboa PortugalDepartment of Tumor Biology and Genetics Medical University of Warsaw Warsaw PolandDepartment of Tumor Biology and Genetics Medical University of Warsaw Warsaw PolandDepartment of Immunology, Genetics and Pathology Uppsala University Uppsala SwedenHematology Department Hospital Universitari i Politècnic la Fe Valencia SpainHematology Department Hospital Universitari i Politècnic la Fe Valencia SpainDepartment of Laboratory Genetics, Genetics and Personalized Clinic Tartu University Hospital Tartu EstoniaDepartment of Laboratory Genetics, Genetics and Personalized Clinic Tartu University Hospital Tartu EstoniaCentre for Molecular Medicine, Central European Institute of Technology (CEITEC) Masaryk University Brno Czech RepublicCentre for Molecular Medicine, Central European Institute of Technology (CEITEC) Masaryk University Brno Czech RepublicWessex Genomics Laboratory Service Salisbury NHS Foundation Trust Salisbury UKWessex Genomics Laboratory Service Salisbury NHS Foundation Trust Salisbury UKDepartment of Hematology University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Center of Salamanca‐IBMCC (USAL‐CSIC) Salamanca SpainDepartment of Hematology University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Cancer Research Center of Salamanca‐IBMCC (USAL‐CSIC) Salamanca SpainB‐Cell Neoplasia Unit and Strategic Research Program on CLL IRCCS Ospedale San Raffaele Milan ItalyB‐Cell Neoplasia Unit and Strategic Research Program on CLL IRCCS Ospedale San Raffaele Milan ItalyCenter for Omics Sciences IRCCS Ospedale San Raffaele Milan ItalyDepartment of Hematology Hospital Universitari Vall d'Hebron (HUVH) Barcelona SpainDepartment of Hematology Hospital Universitari Vall d'Hebron (HUVH) Barcelona SpainOncohematology Research Group, Institute of Biomedical Research of Salamanca (IBSAL) Cancer Research Centre (IBMCC, USAL‐CSIC) and University of Salamanca Salamanca SpainOncohematology Research Group, Institute of Biomedical Research of Salamanca (IBSAL) Cancer Research Centre (IBMCC, USAL‐CSIC) and University of Salamanca Salamanca SpainDepartment of Biological Hematology Sorbonne Université, AP‐HP, Pitié‐Salpêtrière Hospital Paris FranceDepartment of Biological Hematology Sorbonne Université, AP‐HP, Pitié‐Salpêtrière Hospital Paris FranceLaboratório Hemato‐Oncologia Instituto Português de Oncologia de Lisboa Lisbon PortugalDepartment of Hematology Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Complutense University, CNIO, CIBERONC Madrid SpainDepartment of Hematology Hospital Universitari Vall d'Hebron (HUVH) Barcelona SpainHematology laboratory HUPSSD, Hôpital Avicenne, APHP Bobigny FranceMolecular Pathology University Hospitals Dorset Bournemouth UKHaematology Department Belfast City Hospital Belfast UKNational Medical Research Center for Hematology Moscow RussiaDepartment of Molecular Medicine and Surgery Karolinska Institutet Stockholm SwedenDepartment of Hematology Copenhagen University Hospital ‐ Rigshospitalet Copenhagen DenmarkInstitute of Applied Biosciences Centre for Research and Technology Hellas Thessaloniki GreeceB‐Cell Neoplasia Unit and Strategic Research Program on CLL IRCCS Ospedale San Raffaele Milan ItalyDepartment of Internal Medicine, Hematology and Oncology, and Institute of Medical Genetics and Genomics, University Hospital Brno and Medical Faculty Masaryk University Brno Czech RepublicAbstract In chronic lymphocytic leukemia, the reliability of next‐generation sequencing (NGS) to detect TP53 variants ≤10% allelic frequency (low‐VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%, 94.5%, and 94.8% at 1%, 2%, and 3% VAF cut‐off, respectively. While only one false positive (FP) result was reported at >2% VAF, it was more challenging to distinguish true variants <2% VAF from background noise (37 FPs reported by 9 laboratories). The impact of low‐VAF variants on time‐to‐second‐treatment (TTST) and overall survival (OS) was investigated in a series of 1092 patients. Among patients not treated with targeted agents, patients with low‐VAF TP53 variants had shorter TTST and OS versus wt‐TP53 patients, and the relative risk of second‐line treatment or death increased continuously with increasing VAF. Targeted therapy in ≥2 line diminished the difference in OS between patients with low‐VAF TP53 variants and wt‐TP53 patients, while patients with high‐VAF TP53 variants had inferior OS compared to wild type‐TP53 cases. Altogether, NGS‐based approaches are technically capable of detecting low‐VAF variants. No strict threshold can be suggested from a technical standpoint, laboratories reporting TP53 mutations should participate in a standardized validation set‐up. Finally, whereas low‐VAF variants affected outcomes in patients receiving chemoimmunotherapy, their impact on those treated with novel therapies remains undetermined. Our results pave the way for the harmonized and accurate TP53 assessment, which is indispensable for elucidating the role of TP53 mutations in targeted treatment.https://doi.org/10.1002/hem3.70065 |
| spellingShingle | Sarka Pavlova Jitka Malcikova Lenka Radova Silvia Bonfiglio Jack B. Cowland Christian Brieghel Mette K. Andersen Maria Karypidou Bella Biderman Michael Doubek Gregory Lazarian Inmaculada Rapado Matthijs Vynck Naomi A. Porret Martin Andres Dina Rosenberg Dvora Sahar Carolina Martínez‐Laperche Ismael Buño Andrew Hindley David Donaldson Julio B. Sánchez José A. García‐Marco Alicia Serrano‐Alcalá Blanca Ferrer‐Lores Concepción Fernández‐Rodriguez Beatriz Bellosillo Stephan Stilgenbauer Eugen Tausch Hero Nikdin Fiona Quinn Emer Atkinson Lisette van deCorput Cafer Yildiz Cristina Bilbao‐Sieyro Yanira Florido Christian Thiede Caroline Schuster Anastazja Stoj Sylwia Czekalska Anastasia Chatzidimitriou Stamatia Laidou Audrey Bidet Charles Dussiau Friedel Nollet Giovanna Piras Maria Monne Svetlana Smirnova Eugene Nikitin Ivan Sloma Alexis Claudel Laetitia Largeaud Loïc Ysebaert Peter J. M. Valk Amy Christian Renata Walewska David Oscier Marta Sebastião Maria Gomes daSilva Piero Galieni Mario Angelini Davide Rossi Valeria Spina Sónia Matos Vânia Martins Tomasz Stokłosa Monika Pepek Panagiotis Baliakas Rafa Andreu Irene Luna Tiina Kahre Ülle Murumets Tereza Pikousova Terezia Kurucova Sophie Laird Daniel Ward Miguel Alcoceba Ana Balanzategui Lydia Scarfo Francesca Gandini Ettore Zapparoli Adoración Blanco Pau Abrisqueta Ana E. Rodríguez‐Vicente Rocío Benito Clotilde Bravetti Frédéric Davi Paula Gameiro Joaquin Martinez‐Lopez Bárbara Tazón‐Vega Fanny Baran‐Marszak Zadie Davis Mark Catherwood Andrey Sudarikov Richard Rosenquist Carsten U. Niemann Kostas Stamatopoulos Paolo Ghia Sarka Pospisilova Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL HemaSphere |
| title | Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL |
| title_full | Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL |
| title_fullStr | Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL |
| title_full_unstemmed | Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL |
| title_short | Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL |
| title_sort | detection of clinically relevant variants in the tp53 gene below 10 allelic frequency a multicenter study by eric the european research initiative on cll |
| url | https://doi.org/10.1002/hem3.70065 |
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detectionofclinicallyrelevantvariantsinthetp53genebelow10allelicfrequencyamulticenterstudybyerictheeuropeanresearchinitiativeoncll AT paologhia detectionofclinicallyrelevantvariantsinthetp53genebelow10allelicfrequencyamulticenterstudybyerictheeuropeanresearchinitiativeoncll AT sarkapospisilova detectionofclinicallyrelevantvariantsinthetp53genebelow10allelicfrequencyamulticenterstudybyerictheeuropeanresearchinitiativeoncll |