Biallelic loss of GNAS in a patient with pediatric medulloblastoma

Mari J Tokita; Shareef Nahas; Benjamin Briggs; Denise M Malicki; Jill P Mesirov; Iris Anne C Reyes; Lauge Farnaes; Michael L Levy; Stephen F Kingsmore; David Dimmock; John R Crawford; Robert J Wechsler-Reya

doi:10.1101/mcs.a004572

Biallelic loss of GNAS in a patient with pediatric medulloblastoma

Cold Spring Harb Mol Case Stud. 2019 Oct 23;5(5):a004572. doi: 10.1101/mcs.a004572. Print 2019 Oct.

Authors

Mari J Tokita¹, Shareef Nahas¹, Benjamin Briggs^{1

2}, Denise M Malicki^{2

3

4}, Jill P Mesirov^{5

6}, Iris Anne C Reyes¹, Lauge Farnaes¹, Michael L Levy^{7

8}, Stephen F Kingsmore¹, David Dimmock¹, John R Crawford^{2

4

9}, Robert J Wechsler-Reya^{1

2

10}

Affiliations

¹ Rady Children's Institute for Genomic Medicine, San Diego, California 92123, USA.
² Department of Pediatrics and University of California San Diego, San Diego, California 92093, USA.
³ Department of Pathology, University of California San Diego, San Diego, California 92093, USA.
⁴ Rady Children's Hospital San Diego, San Diego, California 92123, USA.
⁵ Department of Medicine and University of California San Diego, La Jolla 92037, California, USA.
⁶ Moores Cancer Center, University of California San Diego, La Jolla 92037, California, USA.
⁷ Division of Pediatric Neurosurgery, Rady Children's Hospital, San Diego, California 92123, USA.
⁸ Department of Neurosurgery and University of California San Diego, San Diego, California 92093, USA.
⁹ Department of Neurosciences, University of California San Diego, San Diego, California 92093, USA.
¹⁰ Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, USA.

Abstract

Genome sequencing was performed on matched normal and tumor tissue from a 6.5-yr-old boy with a diagnosis of recurrent medulloblastoma. A pathogenic heterozygous c.432+1G>A canonical splice donor site variant in GNAS was detected on analysis of blood DNA. Analysis of tumor DNA showed the same splice variant along with copy-neutral loss of heterozygosity on Chromosome 20 encompassing GNAS, consistent with predicted biallelic loss of GNAS in the tumor specimen. This case strengthens the evidence implicating GNAS as a tumor-suppressor gene in medulloblastoma and highlights a scenario in which therapeutics targeting the cAMP pathway may be of great utility.

Keywords: cerebellar medulloblastoma.

Publication types

Case Reports
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Brain Neoplasms / genetics
Cerebellar Neoplasms / genetics
Child
Chromogranins / genetics*
Chromogranins / metabolism
GTP-Binding Protein alpha Subunits, Gs / genetics*
GTP-Binding Protein alpha Subunits, Gs / metabolism
Heterozygote
Humans
Male
Medulloblastoma / genetics*
Medulloblastoma / metabolism

Substances

Chromogranins
GNAS protein, human
GTP-Binding Protein alpha Subunits, Gs

Abstract

Publication types

MeSH terms

Substances

Grants and funding