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A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient

Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presenc...

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Autores principales: Han, Yuyi, Rovella, Valentina, Smirnov, Artem, Buonomo, Oreste Claudio, Mauriello, Alessandro, Perretta, Tommaso, Shi, Yufang, Woodmsith, Jonathan, Bischof, Julia, Melino, Gerry, Candi, Eleonora, Bernassola, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562433/
https://www.ncbi.nlm.nih.gov/pubmed/37813891
http://dx.doi.org/10.1038/s41420-023-01651-3
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author Han, Yuyi
Rovella, Valentina
Smirnov, Artem
Buonomo, Oreste Claudio
Mauriello, Alessandro
Perretta, Tommaso
Shi, Yufang
Woodmsith, Jonathan
Bischof, Julia
Melino, Gerry
Candi, Eleonora
Bernassola, Francesca
author_facet Han, Yuyi
Rovella, Valentina
Smirnov, Artem
Buonomo, Oreste Claudio
Mauriello, Alessandro
Perretta, Tommaso
Shi, Yufang
Woodmsith, Jonathan
Bischof, Julia
Melino, Gerry
Candi, Eleonora
Bernassola, Francesca
author_sort Han, Yuyi
collection PubMed
description Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presence of four somatic mutations in the ephrin type-A receptor 3 (EphA3), TP53, BRCA1-associated protein (BAP1), and MYB genes. The BRCA2, TP53, and BAP1 gene mutations are highly predictive of a defective homologous recombination repair system and subsequent chromosomal instability in this patient. Coherently, the patient displayed a strong homologous recombination deficiency signature and high tumor mutational burden status, which are generally associated with increased probability of immune neoantigens formation and presentation, and with tumor immunogenicity. Analysis of immune checkpoint revealed high expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), programmed death 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), suggesting that the patient might likely benefit from immunotherapies. Altogether, these findings support an unveiled link between BRCA2 inactivation, HR deficiency and increased expression of immune checkpoints in TNBC. This clinical case highlights the importance of screening TNBC patients for genetic mutations and TMB biomarkers in order to predict the potential efficacy of immunotherapy.
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spelling pubmed-105624332023-10-11 A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient Han, Yuyi Rovella, Valentina Smirnov, Artem Buonomo, Oreste Claudio Mauriello, Alessandro Perretta, Tommaso Shi, Yufang Woodmsith, Jonathan Bischof, Julia Melino, Gerry Candi, Eleonora Bernassola, Francesca Cell Death Discov Article Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presence of four somatic mutations in the ephrin type-A receptor 3 (EphA3), TP53, BRCA1-associated protein (BAP1), and MYB genes. The BRCA2, TP53, and BAP1 gene mutations are highly predictive of a defective homologous recombination repair system and subsequent chromosomal instability in this patient. Coherently, the patient displayed a strong homologous recombination deficiency signature and high tumor mutational burden status, which are generally associated with increased probability of immune neoantigens formation and presentation, and with tumor immunogenicity. Analysis of immune checkpoint revealed high expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), programmed death 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), suggesting that the patient might likely benefit from immunotherapies. Altogether, these findings support an unveiled link between BRCA2 inactivation, HR deficiency and increased expression of immune checkpoints in TNBC. This clinical case highlights the importance of screening TNBC patients for genetic mutations and TMB biomarkers in order to predict the potential efficacy of immunotherapy. Nature Publishing Group UK 2023-10-09 /pmc/articles/PMC10562433/ /pubmed/37813891 http://dx.doi.org/10.1038/s41420-023-01651-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Han, Yuyi
Rovella, Valentina
Smirnov, Artem
Buonomo, Oreste Claudio
Mauriello, Alessandro
Perretta, Tommaso
Shi, Yufang
Woodmsith, Jonathan
Bischof, Julia
Melino, Gerry
Candi, Eleonora
Bernassola, Francesca
A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient
title A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient
title_full A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient
title_fullStr A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient
title_full_unstemmed A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient
title_short A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient
title_sort brca2 germline mutation and high expression of immune checkpoints in a tnbc patient
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562433/
https://www.ncbi.nlm.nih.gov/pubmed/37813891
http://dx.doi.org/10.1038/s41420-023-01651-3
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