Improved Molecular Understanding of DIPG Drivers
Improved molecular understanding is needed for rational treatment of diffuse intrinsic pontine gliomas (DIPG). The Koschmann lab is studying mechanisms of tumor progression, tumor evolution and epigenetic regulation in DIPG, using paired and multi-focal sequencing of human DIPG samples, and novel mouse models of DIPG.
In our previous work, we performed multi-focal paired tumor and germline exome DNA and RNA sequencing to uncover the role of phosphatase and tensin homolog (PTEN) loss as an early event in the case of a 6-year-old boy with a DIPG (Koschmann et al, npj Precision Oncology, 2016). This data strengthened the association with PTEN loss in DIPG and provided further argument for the inclusion of PTEN in future targeted sequencing panels for pediatric diffuse intrinsic pontine gliomas and for the development and optimization of mTOR/PI3K inhibitors with optimal central nervous system penetration.
Ongoing work in the Koschmann lab is focused on uncovering and targeting tumor drivers in non-coding regions of the DIPG tumor genome and further exploration of tumor evolution and therapeutic resistance. As well, the Koschmann lab is currently exploring whether novel agents impact DNA damage repair can be employed to target histone alterations in DIPG.