Clonal Analysis of a Case of Multiple Meningiomas Using Multiple Molecular Genetic Approaches: Pathology Case Report

Clonal Analysis of a Case of Multiple Meningiomas Using Multiple Molecular Genetic Approaches:... AbstractOBJECTIVE:Multiple meningiomas are uncommon brain tumors occurring concurrently in several intracranial locations in the same patient. In the present study, we determined the clonality, methylation status of deoxyribonucleic acid, and relationship of genetic alterations in eight meningiomas from one female patient.METHODS:Six molecular genetic techniques, including two methylation-based clonality assays and one transcription-based clonality assay, methylation analysis of CpG islands by methylation-specific polymerase chain reaction, loss of heterozygosity, microsatellite instability, and mutational analysis of the NF2 gene on chromosome 22, were used in comparative investigations on clonality and genetic alterations.RESULTS:The presence of clonal tumor cells was demonstrated by 1) loss of the same copy of chromosome 22 in all eight tumors; 2) transcription of the human AR gene from the same allele in six of eight tumors; 3) a common onmethylated allele at the AR locus in all eight tumors; and 4) the identical single-basepair insertion mutation in exon 9 of the NF2 gene in six of eight tumors. In addition, loss of a copy of the X chromosome in one tumor nodule and microsatellite instability in another nodule were observed.CONCLUSION:Taken together, this case of multiple meningiomas was most likely monoclonal in origin. Loss of chromosome 22 was an early event during the development of multiple meningiomas and was followed by Mutations at the NF2 locus. Later events, including loss of the X chromosome, variation of AR gene expression, or microsatellite instability, may also have played a role in the development of multiple meningiomas in this patient. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Clonal Analysis of a Case of Multiple Meningiomas Using Multiple Molecular Genetic Approaches: Pathology Case Report

Clonal Analysis of a Case of Multiple Meningiomas Using Multiple Molecular Genetic Approaches: Pathology Case Report

PATHOLOGY CASE REPORT en in g io m a s are one of the m ost Clonal Analysis of a Case of Multiple c o m m o n p rim ary intracranial tu ­ m ors (2 0 %) and are thou ght to arise Meningiomas Using Multiple Molecular from cells of the arachnoid and dura m ater in the m en in g es (2, 3). M ultiple Genetic Approaches: Pathology m e n in g io m a s are defined as two or m ore m e n in g io m a s at different in tracra­ Case Report nial locations in the sam e patient ( 11). They m ay occu r in patients w ho have n eu ro fib ro m ato sis T y p e 2 (A/F2), an a u ­ Jay Jiguang Zhu, Ph.D., Takashi Maruyama, M.D., tosom al d o m in a n t genetic disord er a s­ sociated with the form ation of m ultiple Lee B. Jacoby, Ph.D., James G. Herman, Ph.D., tum ors (13). Before the introduction of James F. Gusella, M.D., Peter McL. Black, M.D., Ph.D., com pu ted to m o g ra p h y (CT), m u ltiple Julian K. W u, M.D. m e n in g io m a s w ere reported at an inci­ dence of 1 to 2% of all m e n in g io m a cases Neurosurgical Laboratories and Brain Tumor Center (JJZ, TM, PMB), Brigham and (31). W ith the clinical application of CT Women's Hospital, Boston, Massachusetts; Molecular Neurogenetics Unit (LB), )FG), scans, the o ccu rren ce rate of such tu ­ Massachusetts General Hospital, Charlestown, Massachusetts; Department of m ors has increased to 4.4 to 10.5% (28). Neurosurgery QKW), New England Medical Center, Boston, Massachusetts; Fu rtherm ore, m acro scop ic inspection at Division of Neurosurgery and Brain Tumor Center (JKW), Beth Israel surgery of the dura m ater ad jacen t to Deaconess Medical Center, Boston, Massachusetts; and Oncology Center (JGH), m e n in g io m a s has revealed an in cid en ce The Johns Hopkins Medical Institutions, Baltimore, Maryland of m ultiple m e n in g io m a s of up to 49% (3, 4). C ytogenetic and m o lecu lar genetic OBJECTIVE: M ultiple meningiomas are uncommon brain tumors occurring analyses have d em on strated...
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Publisher
Congress of Neurological Surgeons
Copyright
© Published by Oxford University Press.
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1097/00006123-199908000-00049
Publisher site
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Abstract

AbstractOBJECTIVE:Multiple meningiomas are uncommon brain tumors occurring concurrently in several intracranial locations in the same patient. In the present study, we determined the clonality, methylation status of deoxyribonucleic acid, and relationship of genetic alterations in eight meningiomas from one female patient.METHODS:Six molecular genetic techniques, including two methylation-based clonality assays and one transcription-based clonality assay, methylation analysis of CpG islands by methylation-specific polymerase chain reaction, loss of heterozygosity, microsatellite instability, and mutational analysis of the NF2 gene on chromosome 22, were used in comparative investigations on clonality and genetic alterations.RESULTS:The presence of clonal tumor cells was demonstrated by 1) loss of the same copy of chromosome 22 in all eight tumors; 2) transcription of the human AR gene from the same allele in six of eight tumors; 3) a common onmethylated allele at the AR locus in all eight tumors; and 4) the identical single-basepair insertion mutation in exon 9 of the NF2 gene in six of eight tumors. In addition, loss of a copy of the X chromosome in one tumor nodule and microsatellite instability in another nodule were observed.CONCLUSION:Taken together, this case of multiple meningiomas was most likely monoclonal in origin. Loss of chromosome 22 was an early event during the development of multiple meningiomas and was followed by Mutations at the NF2 locus. Later events, including loss of the X chromosome, variation of AR gene expression, or microsatellite instability, may also have played a role in the development of multiple meningiomas in this patient.

Journal

NeurosurgeryOxford University Press

Published: Aug 1, 1999

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