Frontiers in Oncology (Jan 2020)
Somatic Mosaicism of IDH1 R132H Predisposes to Anaplastic Astrocytoma: A Case of Two Siblings
- Sulgi Lee,
- Sulgi Lee,
- Madhuri Kambhampati,
- M. Isabel Almira-Suarez,
- Cheng-Ying Ho,
- Eshini Panditharatna,
- Seth I. Berger,
- Seth I. Berger,
- Seth I. Berger,
- Seth I. Berger,
- Joyce Turner,
- Joyce Turner,
- David Van Mater,
- Lindsay Kilburn,
- Lindsay Kilburn,
- Roger J. Packer,
- John S. Myseros,
- Eric Vilain,
- Eric Vilain,
- Javad Nazarian,
- Javad Nazarian,
- Javad Nazarian,
- Javad Nazarian,
- Javad Nazarian,
- Miriam Bornhorst,
- Miriam Bornhorst,
- Miriam Bornhorst
Affiliations
- Sulgi Lee
- Center for Genetic Medicine, Children's National Health System, Washington, DC, United States
- Sulgi Lee
- Institute for Biomedical Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- Madhuri Kambhampati
- Center for Genetic Medicine, Children's National Health System, Washington, DC, United States
- M. Isabel Almira-Suarez
- Department of Pathology and Laboratory Medicine, Children's National Health System, Washington, DC, United States
- Cheng-Ying Ho
- Department of Pathology and Neurology, University of Maryland School of Medicine, Baltimore, MD, United States
- Eshini Panditharatna
- Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States
- Seth I. Berger
- Center for Genetic Medicine, Children's National Health System, Washington, DC, United States
- Seth I. Berger
- Department of Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- Seth I. Berger
- Rare Disease Institute, Children's National Health System, Washington, DC, United States
- Seth I. Berger
- Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- Joyce Turner
- Division of Genetics and Metabolism, Children's National Health System, Washington, DC, United States
- Joyce Turner
- 0Division of Oncology, Children's National Health System, Washington, DC, United States
- David Van Mater
- 1Division of Pediatric Hematology Oncology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States
- Lindsay Kilburn
- 0Division of Oncology, Children's National Health System, Washington, DC, United States
- Lindsay Kilburn
- 2Brain Tumor Institute, Children's National Health System, Washington, DC, United States
- Roger J. Packer
- 2Brain Tumor Institute, Children's National Health System, Washington, DC, United States
- John S. Myseros
- 3Division of Neurosurgery, Children's National Health System, Washington, DC, United States
- Eric Vilain
- Center for Genetic Medicine, Children's National Health System, Washington, DC, United States
- Eric Vilain
- Department of Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- Javad Nazarian
- Center for Genetic Medicine, Children's National Health System, Washington, DC, United States
- Javad Nazarian
- Institute for Biomedical Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- Javad Nazarian
- Department of Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- Javad Nazarian
- 2Brain Tumor Institute, Children's National Health System, Washington, DC, United States
- Javad Nazarian
- 4University Children's Hospital Zurich, Zurich, Switzerland
- Miriam Bornhorst
- Center for Genetic Medicine, Children's National Health System, Washington, DC, United States
- Miriam Bornhorst
- 0Division of Oncology, Children's National Health System, Washington, DC, United States
- Miriam Bornhorst
- 2Brain Tumor Institute, Children's National Health System, Washington, DC, United States
- DOI
- https://doi.org/10.3389/fonc.2019.01507
- Journal volume & issue
-
Vol. 9
Abstract
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.
Keywords
- anaplastic astrocytoma
- mosaicism
- cancer predisposition
- ddPCR
- AYA (adolescents and young adults)
- IDH1 R132H mutation
