Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing
IntroductionAccurate identification and characterization of Large Genomic Rearrangements (LGR), especially duplications, are crucial for precise diagnosis and risk assessment. In this report, we characterized an intragenic duplication breakpoint of PALB2 to determine its pathogenicity significance.M...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1355715/full |
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| author | Iulian O. Ban Alice Chabert Thomas Guignard Thomas Guignard Jacques Puechberty Jacques Puechberty Simon Cabello-Aguilar Simon Cabello-Aguilar Pascal Pujol Julie A. Vendrell Jérôme Solassol Jérôme Solassol |
| author_facet | Iulian O. Ban Alice Chabert Thomas Guignard Thomas Guignard Jacques Puechberty Jacques Puechberty Simon Cabello-Aguilar Simon Cabello-Aguilar Pascal Pujol Julie A. Vendrell Jérôme Solassol Jérôme Solassol |
| author_sort | Iulian O. Ban |
| collection | DOAJ |
| description | IntroductionAccurate identification and characterization of Large Genomic Rearrangements (LGR), especially duplications, are crucial for precise diagnosis and risk assessment. In this report, we characterized an intragenic duplication breakpoint of PALB2 to determine its pathogenicity significance.MethodsA 52-year-old female with triple-negative breast cancer was diagnosed with a novel PALB2 LGR. An efficient and accurate methodology was applied, combining long-read sequencing and transcript analysis for the rapid characterization of the duplication.ResultsDuplication of exons 5 and 6 of PALB2 was validated by transcript analysis. Long-read sequencing enabled the localization of breakpoints within Alu elements, providing insights into the mechanism of duplication via non-allelic homologous recombination.ConclusionUsing our combined methodology, we reclassified the PALB2 duplication as a pathogenic variant. This reclassification suggests a possible causative link between this specific genetic alteration and the aggressive phenotype of the patient. |
| first_indexed | 2024-03-07T20:02:58Z |
| format | Article |
| id | doaj.art-476bc9d5b9164fcab4492b6136f55df5 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-07T20:02:58Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-476bc9d5b9164fcab4492b6136f55df52024-02-28T05:16:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-02-011410.3389/fonc.2024.13557151355715Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencingIulian O. Ban0Alice Chabert1Thomas Guignard2Thomas Guignard3Jacques Puechberty4Jacques Puechberty5Simon Cabello-Aguilar6Simon Cabello-Aguilar7Pascal Pujol8Julie A. Vendrell9Jérôme Solassol10Jérôme Solassol11Laboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, Centre Hospitalier Universitaire (CHU) Montpellier, Université de Montpellier, Montpellier, FranceLaboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, Centre Hospitalier Universitaire (CHU) Montpellier, Université de Montpellier, Montpellier, FranceDepartment of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier, FranceLaboratoire de Génétique Chromosomique, Plateforme ChromoStem, Centre Hospitalier Universitaire (CHU) de Montpellier, Université de Montpellier, Montpellier, FranceDepartment of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier, FranceLaboratoire de Génétique Chromosomique, Plateforme ChromoStem, Centre Hospitalier Universitaire (CHU) de Montpellier, Université de Montpellier, Montpellier, FranceLaboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, Centre Hospitalier Universitaire (CHU) Montpellier, Université de Montpellier, Montpellier, FranceMontpellier BioInformatics for Clinical Diagnosis (MOBIDIC), Molecular Medicine and Genomics Platform (PMMG), Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier, FranceDepartment of Medical Genetics, Arnaud de Villeneuve Hospital, Montpellier, FranceLaboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, Centre Hospitalier Universitaire (CHU) Montpellier, Université de Montpellier, Montpellier, FranceLaboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, Centre Hospitalier Universitaire (CHU) Montpellier, Université de Montpellier, Montpellier, FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM), Univ Montpellier, Inserm, Institut du Cancer de Montpellier (ICM), Montpellier, FranceIntroductionAccurate identification and characterization of Large Genomic Rearrangements (LGR), especially duplications, are crucial for precise diagnosis and risk assessment. In this report, we characterized an intragenic duplication breakpoint of PALB2 to determine its pathogenicity significance.MethodsA 52-year-old female with triple-negative breast cancer was diagnosed with a novel PALB2 LGR. An efficient and accurate methodology was applied, combining long-read sequencing and transcript analysis for the rapid characterization of the duplication.ResultsDuplication of exons 5 and 6 of PALB2 was validated by transcript analysis. Long-read sequencing enabled the localization of breakpoints within Alu elements, providing insights into the mechanism of duplication via non-allelic homologous recombination.ConclusionUsing our combined methodology, we reclassified the PALB2 duplication as a pathogenic variant. This reclassification suggests a possible causative link between this specific genetic alteration and the aggressive phenotype of the patient.https://www.frontiersin.org/articles/10.3389/fonc.2024.1355715/fullPALB2LGRbreast cancerlong-read sequencingmolecular alteration |
| spellingShingle | Iulian O. Ban Alice Chabert Thomas Guignard Thomas Guignard Jacques Puechberty Jacques Puechberty Simon Cabello-Aguilar Simon Cabello-Aguilar Pascal Pujol Julie A. Vendrell Jérôme Solassol Jérôme Solassol Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing Frontiers in Oncology PALB2 LGR breast cancer long-read sequencing molecular alteration |
| title | Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing |
| title_full | Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing |
| title_fullStr | Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing |
| title_full_unstemmed | Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing |
| title_short | Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing |
| title_sort | characterizing palb2 intragenic duplication breakpoints in a triple negative breast cancer case using long read sequencing |
| topic | PALB2 LGR breast cancer long-read sequencing molecular alteration |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1355715/full |
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