TY - JOUR
T1 - Somatic Mosaicism of IDH1 R132H Predisposes to Anaplastic Astrocytoma
T2 - A Case of Two Siblings
AU - Lee, Sulgi
AU - Kambhampati, Madhuri
AU - Almira-Suarez, M. Isabel
AU - Ho, Cheng Ying
AU - Panditharatna, Eshini
AU - Berger, Seth I.
AU - Turner, Joyce
AU - Van Mater, David
AU - Kilburn, Lindsay
AU - Packer, Roger J.
AU - Myseros, John S.
AU - Vilain, Eric
AU - Nazarian, Javad
AU - Bornhorst, Miriam
N1 - Funding Information:
This work was supported by funding from Smashing Walnuts Foundation (Leesburg, VA), Isabella Kerr Molina Foundation (London, UK), The Cure Starts Now Foundation (Cincinnati, OH), Gift from a Child—The Swifty Foundation (Woodridge, IL), DIPG Collaborative (Cincinnati, OH), Musella Foundation (Hewlett, NY), The Matthew Larson Foundation for Pediatric Brain Tumors (Franklin Lake, NJ), The Lilabean Foundation
Funding Information:
The authors would like acknowledge the generosity of the patients and their families. We would also like to thank the staff members of Duke University Health System Department of Pathology and Laboratory services, especially Dr. Roger McLendon and Kimberly Isley, for sharing specimens for this study. Funding. This work was supported by funding from Smashing Walnuts Foundation (Leesburg, VA), Isabella Kerr Molina Foundation (London, UK), The Cure Starts Now Foundation (Cincinnati, OH), Gift from a Child—The Swifty Foundation (Woodridge, IL), DIPG Collaborative (Cincinnati, OH), Musella Foundation (Hewlett, NY), The Matthew Larson Foundation for Pediatric Brain Tumors (Franklin Lake, NJ), The Lilabean Foundation for Pediatric brain Cancer Research (Silver Spring, MD), Rally Foundation (Atlanta, GA).
Publisher Copyright:
© Copyright © 2020 Lee, Kambhampati, Almira-Suarez, Ho, Panditharatna, Berger, Turner, Van Mater, Kilburn, Packer, Myseros, Vilain, Nazarian and Bornhorst.
PY - 2020/1/14
Y1 - 2020/1/14
N2 - Anaplastic astrocytomas are aggressive glial cancers that present poor prognosis and high recurrence. Heterozygous IDH1 R132H mutations are common in adolescent and young adult anaplastic astrocytomas. In a majority of cases, the IDH1 R132H mutation is unique to the tumor, although rare cases of anaplastic astrocytoma have been described in patients with mosaic IDH1 mutations (Ollier disease or Maffucci syndrome). Here, we present two siblings with IDH1 R132H mutant high grade astrocytomas diagnosed at 14 and 26 years of age. Analysis of IDHR132H mutations in the siblings' tumors and non-neoplastic tissues, including healthy regions of the brain, cheek cells, and primary teeth indicate mosaicism of IDHR132H. Whole exome sequencing of the tumor tissue did not reveal any other common mutations between the two siblings. This study demonstrates the first example of IDH1 R132H mosaicism, acquired during early development, that provides an alternative mechanism of cancer predisposition.
AB - Anaplastic astrocytomas are aggressive glial cancers that present poor prognosis and high recurrence. Heterozygous IDH1 R132H mutations are common in adolescent and young adult anaplastic astrocytomas. In a majority of cases, the IDH1 R132H mutation is unique to the tumor, although rare cases of anaplastic astrocytoma have been described in patients with mosaic IDH1 mutations (Ollier disease or Maffucci syndrome). Here, we present two siblings with IDH1 R132H mutant high grade astrocytomas diagnosed at 14 and 26 years of age. Analysis of IDHR132H mutations in the siblings' tumors and non-neoplastic tissues, including healthy regions of the brain, cheek cells, and primary teeth indicate mosaicism of IDHR132H. Whole exome sequencing of the tumor tissue did not reveal any other common mutations between the two siblings. This study demonstrates the first example of IDH1 R132H mosaicism, acquired during early development, that provides an alternative mechanism of cancer predisposition.
KW - AYA (adolescents and young adults)
KW - IDH1 R132H mutation
KW - anaplastic astrocytoma
KW - cancer predisposition
KW - ddPCR
KW - mosaicism
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UR - http://www.scopus.com/inward/citedby.url?scp=85078728080&partnerID=8YFLogxK
U2 - 10.3389/fonc.2019.01507
DO - 10.3389/fonc.2019.01507
M3 - Article
AN - SCOPUS:85078728080
SN - 2234-943X
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1507
ER -