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NPJ Precis Oncol. 2017 Sep 14;1(1):32. doi: 10.1038/s41698-017-0033-y. eCollection 2017.

Multi-focal sequencing of a diffuse intrinsic pontine glioma establishes PTEN loss as an early event.

Author information

1
Department of Pediatrics, Division of Pediatric Hematology/Oncology, Michigan Medicine, Ann Arbor, MI 48109 USA.
2
Department of Pathology, Michigan Medicine, Ann Arbor, MI 48109 USA.
3
Michigan Center for Translational Pathology, Michigan Medicine, Ann Arbor, MI 48109 USA.
4
Comprehensive Cancer Center, Michigan Medicine, Ann Arbor, MI 48109 USA.
5
5Howard Hughes Medical Institute, Michigan Medicine, Ann Arbor, MI 48109 USA.
6
Department of Neurosurgery, Michigan Medicine, Ann Arbor, MI 48109 USA.
7
Department of Cell and Developmental Biology, Michigan Medicine, Ann Arbor, MI 48109 USA.
8
Department of Pediatrics, Division of Pediatric Neurology, Michigan Medicine, Ann Arbor, MI 48109 USA.

Abstract

Improved molecular understanding is needed for rational treatment of diffuse intrinsic pontine gliomas (DIPG). Here, using multi-focal paired tumor and germline exome DNA and RNA sequencing, we uncovered phosphatase and tensin homolog (PTEN) loss as a clonal mutation in the case of a 6-year-old boy with a diffuse intrinsic pontine glioma, and incorporated copy number alteration analyses to provide a more detailed understanding of clonal evolution in diffuse intrinsic pontine gliomas. As well, using the PedcBioPortal, we found alterations in PTEN in 16 of 326 (4.9%) cases of pediatric high-grade glioma (3 of 154 (1.9%) brainstem) for which full sequencing data was available. Our data strengthens the association with PTEN loss in diffuse intrinsic pontine gliomas and provides 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.

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