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

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Authors

PÁLOVÁ Hana DAS Anirban POKORNÁ Petra BAJČIOVÁ Viera PAVELKA Zdenek JEŽOVÁ Marta PÁL Karol DIMAYACYAC Jose R NEGM Logine STENGS Lucie BIANCHI Vanessa VEJMĚLKOVÁ Klára NOSKOVÁ Kristýna JAROŠOVÁ Marie MEJSTŘÍKOVÁ Soňa MÚDRY Peter KÝR Michal MERTA Tomáš TINKA Pavel DRÁBOVÁ Klára AULICKÁ Štefánia JUGAS Robin TABORI Uri SLABÝ Ondřej ŠTĚRBA Jaroslav

Year of publication 2024
Type Article in Periodical
Magazine / Source NPJ PRECISION ONCOLOGY
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.nature.com/articles/s41698-024-00597-8
Doi http://dx.doi.org/10.1038/s41698-024-00597-8
Keywords malignant tumor; constitutional mismatch repair deficiency syndrome
Attached files
Description 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.
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