Oncotarget

Research Papers:

Angiomatous meningiomas have a distinct genetic profile with multiple chromosomal polysomies including polysomy of chromosome 5

Malak S. Abedalthagafi, Parker H. Merrill, Wenya Linda Bi, Robert T. Jones, Marc L. Listewnik, Shakti H. Ramkissoon, Aaron R. Thorner, Ian F. Dunn, Rameen Beroukhim, Brian M. Alexander, Priscilla K. Brastianos, Joshua M. Francis, Rebecca D. Folkerth, Keith L. Ligon, Paul Van Hummelen, Azra H. Ligon and Sandro Santagata _

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Oncotarget. 2014; 5:10596-10606. https://doi.org/10.18632/oncotarget.2517

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Abstract

Malak S. Abedalthagafi1, Parker H. Merrill1, Wenya Linda Bi2, Robert T. Jones1, Marc L. Listewnik3, Shakti H. Ramkissoon1, Aaron R. Thorner4,5, Ian F. Dunn2, Rameen Beroukhim4,6,9, Brian M. Alexander7, Priscilla K. Brastianos4,6,8, Joshua M. Francis4,6, Rebecca D. Folkerth1, Keith L. Ligon1,4, Paul Van Hummelen4,5, Azra H. Ligon3 and Sandro Santagata1,9

1 Department of Pathology, Division of Neuropathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

2 Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

3 Clinical Cytogenetics Laboratory, Center for Advanced Molecular Diagnostics, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

4 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

5 Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA

6 Broad Institute of MIT and Harvard, Cambridge, MA, USA

7 Department of Radiation Oncology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

8 Department of Neuro-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

9 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA

Correspondence:

Sandro Santagata, email:

Keywords: meningioma, angiomatous, polysomy, aCGH, molecular diagnostics, Next Generation Sequencing

Received: September 14, 2014 Accepted: September 24, 2014 Published: September 25, 2014

Abstract

Meningiomas are a diverse group of tumors with a broad spectrum of histologic features. There are over 12 variants of meningioma, whose genetic features are just beginning to be described. Angiomatous meningioma is a World Health Organization (WHO) meningioma variant with a predominance of blood vessels. They are uncommon and confirming the histopathologic classification can be challenging. Given a lack of biomarkers that define the angiomatous subtype and limited understanding of the genetic changes underlying its tumorigenesis, we compared the genomic characteristics of angiomatous meningioma to more common meningioma subtypes. While typical grade I meningiomas demonstrate monosomy of chromosome 22 or lack copy number aberrations, 13 of 14 cases of angiomatous meningioma demonstrated a distinct copy number profile – polysomies of at least one chromosome, but often of many, especially in chromosomes 5, 13, and 20. WHO grade II atypical meningiomas with angiomatous features have both polysomies and genetic aberrations characteristic of other atypical meningiomas. Sequencing of over 560 cancer-relevant genes in 16 cases of angiomatous meningioma showed that these tumors lack common mutations found in other variants of meningioma. Our study demonstrates that angiomatous meningiomas have distinct genomic features that may be clinically useful for their diagnosis.


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