Establishment and molecular profiling of a PDX model of a metachronous brain tumor in a patient with constitutional mismatch repair deficiency with biallelic MSH6 variant.

ABSTRACT:

Background

Constitutional mismatch repair deficiency (CMMRD) is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes. This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft (PDX) from a Brazilian child with CMMRD.

Methods

After PDX development, methylation array, whole exome sequencing, and NanoString techniques were applied to describe the genetic landscape of CMMRD.

Results

A 6½-year-old girl was diagnosed with Sonic Hedgehog (SHH)-activated medulloblastoma and somatic TP53-mutant. After surgery and radiochemotherapy, she remained free of disease progression. At 10 years and 3 months, she developed a diffuse pediatric-type high-grade glioma (dpHGG). The child had a family

SUBMITTER: Moreno DA 

PROVIDER: S-EPMC12746185 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature