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
- case report
- copy number
- end stage renal disease
- lymph node metastasis
- ejection fraction
- newly diagnosed
- intellectual disability
- risk factors
- high resolution
- palliative care
- genome wide identification
- radiation therapy
- dna methylation
- gene expression
- childhood cancer
- patient reported outcomes
- oxidative stress
- transcription factor
- single molecule
- middle aged