Precision immuno-oncology approach for four malignant tumors in siblings with constitutional mismatch repair deficiency syndrome.
NPJ Precis Oncol
; 8(1): 110, 2024 May 21.
Article
in En
| MEDLINE
| ID: mdl-38773265
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
NPJ Precis Oncol
Year:
2024
Type:
Article
Affiliation country:
Czech Republic