Somatic Mosaicism of IDH1 R132H Predisposes to Anaplastic Astrocytoma: A Case of Two Siblings

Sulgi Lee; Madhuri Kambhampati; M. Isabel Almira-Suarez; Cheng Ying Ho; Eshini Panditharatna; Seth I. Berger; Joyce Turner; David Van Mater; Lindsay Kilburn; Roger J. Packer; John S. Myseros; Eric Vilain; Javad Nazarian; Miriam Bornhorst

doi:10.3389/fonc.2019.01507

Somatic Mosaicism of IDH1 R132H Predisposes to Anaplastic Astrocytoma: A Case of Two Siblings

Sulgi Lee, Madhuri Kambhampati, M. Isabel Almira-Suarez, Cheng Ying Ho, Eshini Panditharatna, Seth I. Berger, Joyce Turner, David Van Mater, Lindsay Kilburn, Roger J. Packer, John S. Myseros, Eric Vilain, Javad Nazarian^*, Miriam Bornhorst

^*Corresponding author for this work

Pediatrics

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

2 Scopus citations

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 IDH^R132H mutations in the siblings' tumors and non-neoplastic tissues, including healthy regions of the brain, cheek cells, and primary teeth indicate mosaicism of IDH^R132H. 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.

Original language	English (US)
Article number	1507
Journal	Frontiers in Oncology
Volume	9
DOIs	https://doi.org/10.3389/fonc.2019.01507
State	Published - Jan 14 2020

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 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).

Keywords

AYA (adolescents and young adults)
IDH1 R132H mutation
anaplastic astrocytoma
cancer predisposition
ddPCR
mosaicism

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fonc.2019.01507

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Lee, S., Kambhampati, M., Almira-Suarez, M. I., Ho, C. Y., Panditharatna, E., Berger, S. I., Turner, J., Van Mater, D., Kilburn, L., Packer, R. J., Myseros, J. S., Vilain, E., Nazarian, J., & Bornhorst, M. (2020). Somatic Mosaicism of IDH1 R132H Predisposes to Anaplastic Astrocytoma: A Case of Two Siblings. Frontiers in Oncology, 9, Article 1507. https://doi.org/10.3389/fonc.2019.01507

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title = "Somatic Mosaicism of IDH1 R132H Predisposes to Anaplastic Astrocytoma: A Case of Two Siblings",

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.",

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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

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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.

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Somatic Mosaicism of IDH1 R132H Predisposes to Anaplastic Astrocytoma: A Case of Two Siblings

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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