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Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle

The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clini...

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Autores principales: Lin, Frank Y., Bergstrom, Katie, Person, Richard, Bavle, Abhishek, Ballester, Leomar Y., Scollon, Sarah, Raesz-Martinez, Robin, Jea, Andrew, Birchansky, Sherri, Wheeler, David A., Berg, Stacey L., Chintagumpala, Murali M., Adesina, Adekunle M., Eng, Christine, Roy, Angshumoy, Plon, Sharon E., Parsons, D. Williams
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002928/
https://www.ncbi.nlm.nih.gov/pubmed/27626068
http://dx.doi.org/10.1101/mcs.a001057
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author Lin, Frank Y.
Bergstrom, Katie
Person, Richard
Bavle, Abhishek
Ballester, Leomar Y.
Scollon, Sarah
Raesz-Martinez, Robin
Jea, Andrew
Birchansky, Sherri
Wheeler, David A.
Berg, Stacey L.
Chintagumpala, Murali M.
Adesina, Adekunle M.
Eng, Christine
Roy, Angshumoy
Plon, Sharon E.
Parsons, D. Williams
author_facet Lin, Frank Y.
Bergstrom, Katie
Person, Richard
Bavle, Abhishek
Ballester, Leomar Y.
Scollon, Sarah
Raesz-Martinez, Robin
Jea, Andrew
Birchansky, Sherri
Wheeler, David A.
Berg, Stacey L.
Chintagumpala, Murali M.
Adesina, Adekunle M.
Eng, Christine
Roy, Angshumoy
Plon, Sharon E.
Parsons, D. Williams
author_sort Lin, Frank Y.
collection PubMed
description The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care.
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spelling pubmed-50029282016-09-13 Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle Lin, Frank Y. Bergstrom, Katie Person, Richard Bavle, Abhishek Ballester, Leomar Y. Scollon, Sarah Raesz-Martinez, Robin Jea, Andrew Birchansky, Sherri Wheeler, David A. Berg, Stacey L. Chintagumpala, Murali M. Adesina, Adekunle M. Eng, Christine Roy, Angshumoy Plon, Sharon E. Parsons, D. Williams Cold Spring Harb Mol Case Stud Research Report The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care. Cold Spring Harbor Laboratory Press 2016-09 /pmc/articles/PMC5002928/ /pubmed/27626068 http://dx.doi.org/10.1101/mcs.a001057 Text en © 2016 Lin 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 Research Report
Lin, Frank Y.
Bergstrom, Katie
Person, Richard
Bavle, Abhishek
Ballester, Leomar Y.
Scollon, Sarah
Raesz-Martinez, Robin
Jea, Andrew
Birchansky, Sherri
Wheeler, David A.
Berg, Stacey L.
Chintagumpala, Murali M.
Adesina, Adekunle M.
Eng, Christine
Roy, Angshumoy
Plon, Sharon E.
Parsons, D. Williams
Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle
title Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle
title_full Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle
title_fullStr Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle
title_full_unstemmed Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle
title_short Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle
title_sort integrated tumor and germline whole-exome sequencing identifies mutations in mapk and pi3k pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002928/
https://www.ncbi.nlm.nih.gov/pubmed/27626068
http://dx.doi.org/10.1101/mcs.a001057
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