Abstract
Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 614-620 |
| Number of pages | 7 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 59 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jan 1 2000 |
| Externally published | Yes |
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Keywords
- Loss of heterozygosity
- Meningioma
- NF2 mutations
- Radiation
- Tumor suppressor genes
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience
Cite this
Radiation-induced meningioma : A distinct molecular genetic pattern? / Shoshan, Yigal; Chernova, Olga; Jeun, Sin Soo; Somerville, Robert P.; Israel, Zvi; Barnett, Gene H.; Cowell, John Kenneth.
In: Journal of Neuropathology and Experimental Neurology, Vol. 59, No. 7, 01.01.2000, p. 614-620.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Radiation-induced meningioma
T2 - A distinct molecular genetic pattern?
AU - Shoshan, Yigal
AU - Chernova, Olga
AU - Jeun, Sin Soo
AU - Somerville, Robert P.
AU - Israel, Zvi
AU - Barnett, Gene H.
AU - Cowell, John Kenneth
PY - 2000/1/1
Y1 - 2000/1/1
N2 - Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors.
AB - Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors.
KW - Loss of heterozygosity
KW - Meningioma
KW - NF2 mutations
KW - Radiation
KW - Tumor suppressor genes
UR - http://www.scopus.com/inward/record.url?scp=0033947952&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033947952&partnerID=8YFLogxK
U2 - 10.1093/jnen/59.7.614
DO - 10.1093/jnen/59.7.614
M3 - Review article
VL - 59
SP - 614
EP - 620
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 7
ER -