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...
Loading next page...
 
/lp/ou_press/clonal-analysis-of-a-case-of-multiple-meningiomas-using-multiple-aHtEztnWJy
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
See Article on Publisher Site

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

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off