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
- copy number
- case report
- end stage renal disease
- replacement therapy
- chronic kidney disease
- newly diagnosed
- intellectual disability
- palliative care
- genome wide identification
- ejection fraction
- dna methylation
- lymph node metastasis
- risk factors
- childhood cancer
- autism spectrum disorder
- diffuse large b cell lymphoma
- early onset
- prognostic factors
- radiation therapy
- middle aged
- dna repair
- transcription factor
- single molecule