Biallelic loss of GNAS in a patient with pediatric medulloblastoma

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 spl...

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Autores principales: Tokita, Mari J., Nahas, Shareef, Briggs, Benjamin, Malicki, Denise M., Mesirov, Jill P., Reyes, Iris Anne C., Farnaes, Lauge, Levy, Michael L., Kingsmore, Stephen F., Dimmock, David, Crawford, John R., Wechsler-Reya, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2019
Materias:
Rapid Cancer Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824258/
https://www.ncbi.nlm.nih.gov/pubmed/31624069
http://dx.doi.org/10.1101/mcs.a004572
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author Tokita, Mari J.
Nahas, Shareef
Briggs, Benjamin
Malicki, Denise M.
Mesirov, Jill P.
Reyes, Iris Anne C.
Farnaes, Lauge
Levy, Michael L.
Kingsmore, Stephen F.
Dimmock, David
Crawford, John R.
Wechsler-Reya, Robert J.
author_facet Tokita, Mari J.
Nahas, Shareef
Briggs, Benjamin
Malicki, Denise M.
Mesirov, Jill P.
Reyes, Iris Anne C.
Farnaes, Lauge
Levy, Michael L.
Kingsmore, Stephen F.
Dimmock, David
Crawford, John R.
Wechsler-Reya, Robert J.
author_sort Tokita, Mari J.
collection PubMed
description 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.
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spelling pubmed-68242582019-11-15 Biallelic loss of GNAS in a patient with pediatric medulloblastoma Tokita, Mari J. Nahas, Shareef Briggs, Benjamin Malicki, Denise M. Mesirov, Jill P. Reyes, Iris Anne C. Farnaes, Lauge Levy, Michael L. Kingsmore, Stephen F. Dimmock, David Crawford, John R. Wechsler-Reya, Robert J. Cold Spring Harb Mol Case Stud Rapid Cancer Communication 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. Cold Spring Harbor Laboratory Press 2019-10 /pmc/articles/PMC6824258/ /pubmed/31624069 http://dx.doi.org/10.1101/mcs.a004572 Text en © 2019 Tokita et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
spellingShingle Rapid Cancer Communication
Tokita, Mari J.
Nahas, Shareef
Briggs, Benjamin
Malicki, Denise M.
Mesirov, Jill P.
Reyes, Iris Anne C.
Farnaes, Lauge
Levy, Michael L.
Kingsmore, Stephen F.
Dimmock, David
Crawford, John R.
Wechsler-Reya, Robert J.
Biallelic loss of GNAS in a patient with pediatric medulloblastoma
title Biallelic loss of GNAS in a patient with pediatric medulloblastoma
title_full Biallelic loss of GNAS in a patient with pediatric medulloblastoma
title_fullStr Biallelic loss of GNAS in a patient with pediatric medulloblastoma
title_full_unstemmed Biallelic loss of GNAS in a patient with pediatric medulloblastoma
title_short Biallelic loss of GNAS in a patient with pediatric medulloblastoma
title_sort biallelic loss of gnas in a patient with pediatric medulloblastoma
topic Rapid Cancer Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824258/
https://www.ncbi.nlm.nih.gov/pubmed/31624069
http://dx.doi.org/10.1101/mcs.a004572
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