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

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

Pediatrics

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English
Journal	Cold Spring Harbor Molecular Case Studies
Volume	5
Issue number	5
DOIs	https://doi.org/10.1101/mcs.a004572
State	Published - Oct 2019

Keywords

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

Access to Document

10.1101/mcs.a004572

Cite this

@article{7039111a8ade42c6b1f8fcdc44a5ed66,

title = "Biallelic loss of GNAS in a patient with pediatric medulloblastoma",

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

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

note = "{\textcopyright} 2019 Tokita et al.; Published by Cold Spring Harbor Laboratory Press.",

year = "2019",

month = oct,

doi = "10.1101/mcs.a004572",

language = "English",

volume = "5",

journal = "Cold Spring Harbor Molecular Case Studies",

issn = "2373-2873",

publisher = "Cold Spring Harbor Laboratory Press",

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T1 - Biallelic loss of GNAS in a patient with pediatric medulloblastoma

AU - Tokita, Mari J

AU - Nahas, Shareef

AU - Briggs, Benjamin

AU - Malicki, Denise M

AU - Mesirov, Jill P

AU - Reyes, Iris Anne C

AU - Farnaes, Lauge

AU - Levy, Michael L

AU - Kingsmore, Stephen F

AU - Dimmock, David

AU - Crawford, John R

AU - Wechsler-Reya, Robert J

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - Alleles

KW - Brain Neoplasms/genetics

KW - Cerebellar Neoplasms/genetics

KW - Child

KW - Chromogranins/genetics

KW - GTP-Binding Protein alpha Subunits, Gs/genetics

KW - Heterozygote

KW - Humans

KW - Male

KW - Medulloblastoma/genetics

U2 - 10.1101/mcs.a004572

DO - 10.1101/mcs.a004572

M3 - Article

C2 - 31624069

SN - 2373-2873

VL - 5

JO - Cold Spring Harbor Molecular Case Studies

JF - Cold Spring Harbor Molecular Case Studies

IS - 5

ER -