Precision immuno-oncology approach for four malignant tumors in siblings with constitutional mismatch repair deficiency syndrome.

Journal

NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166

Informations de publication

Date de publication:
21 May 2024
Historique:
received: 20 10 2023
accepted: 03 05 2024
medline: 22 5 2024
pubmed: 22 5 2024
entrez: 21 5 2024
Statut: epublish

Résumé

Constitutional mismatch repair deficiency (CMMRD) is a rare syndrome characterized by an increased incidence of cancer. It is caused by biallelic germline mutations in one of the four mismatch repair genes (MMR) genes: MLH1, MSH2, MSH6, or PMS2. Accurate diagnosis accompanied by a proper molecular genetic examination plays a crucial role in cancer management and also has implications for other family members. In this report, we share the impact of the diagnosis and challenges during the clinical management of two brothers with CMMRD from a non-consanguineous family harbouring compound heterozygous variants in the PMS2 gene. Both brothers presented with different phenotypic manifestations and cancer spectrum. Treatment involving immune checkpoint inhibitors significantly contributed to prolonged survival in both patients affected by lethal gliomas. The uniform hypermutation also allowed immune-directed treatment using nivolumab for the B-cell lymphoma, thereby limiting the intensive chemotherapy exposure in this young patient who remains at risk for subsequent malignancies.

Identifiants

DOI: 10.1038/s41698-024-00597-8 PMID: 38773265
pubmed: 38773265
doi: 10.1038/s41698-024-00597-8
pii: 10.1038/s41698-024-00597-8
doi:

Types de publication

Journal Article

Langues

eng

Pagination

110

Informations de copyright

© 2024. The Author(s).

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Auteurs

Hana Palova (H)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
ORCID: 0000-0001-8803-9433

Anirban Das (A)

Division of Haematology Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.

Petra Pokorna (P)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
ORCID: 0000-0003-1037-878X

Viera Bajciova (V)

Department of Pediatric Oncology, University Hospital Brno, and Faculty of Medicine, ERN PaedCan Center, Masaryk University, Brno, Czech Republic.

Zdenek Pavelka (Z)

Department of Pediatric Oncology, University Hospital Brno, and Faculty of Medicine, ERN PaedCan Center, Masaryk University, Brno, Czech Republic.

Marta Jezova (M)

Department of Pathology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Karol Pal (K)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
ORCID: 0000-0002-7726-4691

Jose R Dimayacyac (JR)

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.

Logine Negm (L)

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
ORCID: 0009-0006-9059-3824

Lucie Stengs (L)

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.

Vanessa Bianchi (V)

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.

Klara Vejmelkova (K)

Department of Pediatric Oncology, University Hospital Brno, and Faculty of Medicine, ERN PaedCan Center, Masaryk University, Brno, Czech Republic.

Kristyna Noskova (K)

Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Clinical Pharmacy Section of Hospital Pharmacy, University Hospital Brno, Brno, Czech Republic.

Marie Jarosova (M)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Sona Mejstrikova (S)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Peter Mudry (P)

Department of Pediatric Oncology, University Hospital Brno, and Faculty of Medicine, ERN PaedCan Center, Masaryk University, Brno, Czech Republic.

Michal Kyr (M)

Department of Pediatric Oncology, University Hospital Brno, and Faculty of Medicine, ERN PaedCan Center, Masaryk University, Brno, Czech Republic.

Tomas Merta (T)

Department of Pediatric Oncology, University Hospital Brno, and Faculty of Medicine, ERN PaedCan Center, Masaryk University, Brno, Czech Republic.

Pavel Tinka (P)

Department of Pediatric Oncology, University Hospital Brno, and Faculty of Medicine, ERN PaedCan Center, Masaryk University, Brno, Czech Republic.

Klara Drabova (K)

Institute of Medical Genetics and Genomics, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Stefania Aulicka (S)

Department of Pediatric Neurology, University Hospital Brno, and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Robin Jugas (R)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
ORCID: 0000-0003-4675-0985

Uri Tabori (U)

Division of Haematology Oncology, The Hospital for Sick Children, Toronto, ON, Canada.
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.

Ondrej Slaby (O)

Central European Institute of Technology, Masaryk University, Brno, Czech Republic. oslaby@med.muni.cz.
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. oslaby@med.muni.cz.

Jaroslav Sterba (J)

Department of Pediatric Oncology, University Hospital Brno, and Faculty of Medicine, ERN PaedCan Center, Masaryk University, Brno, Czech Republic. sterba.jaroslav@fnbrno.cz.
ORCID: 0000-0002-8482-8352

Classifications MeSH