Precision immuno-oncology approach for four malignant tumors in siblings with constitutional mismatch repair deficiency syndrome.
Hana PalovaAnirban DasPetra PokornaViera BajciovaZdenek PavelkaMarta JezovaKarol PalJose R DimayacyacLogine NegmLucie StengsVanessa BianchiKlara VejmelkovaKristyna NoskovaMarie JarosovaSona MejstrikovaPeter MudryMichal KyrTomas MertaPavel TinkaKlara DrabovaStefania AulickaRobin JugasUri TaboriOndrej SlabyJaroslav SterbaPublished in: NPJ precision oncology (2024)
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.
Keyphrases
- papillary thyroid
- genome wide
- squamous cell
- end stage renal disease
- copy number
- case report
- chronic kidney disease
- newly diagnosed
- intellectual disability
- dna methylation
- squamous cell carcinoma
- prognostic factors
- gene expression
- childhood cancer
- high resolution
- replacement therapy
- high grade
- early onset
- peritoneal dialysis
- combination therapy
- autism spectrum disorder
- mass spectrometry
- patient reported outcomes