TY - JOUR
T1 - Loss of heterozygosity reveals non-VHL allelic loss in hemangioblastomas at 22q13
AU - Beckner, Marie E.
AU - Sasatomi, Eizaburo
AU - Swalsky, Patricia A.
AU - Hamilton, Ronald L.
AU - Pollack, Ian F.
AU - Finkelstein, Sydney D.
N1 - Funding Information:
The authors thank Leslie Viramontes, HT(ASCP), and colleagues, University of Pittsburgh Medical Center Immunohistochemistry Laboratory, for performing special stains; Dr Douglas E. Moul, Department of Psychiatry, University of Pittsburgh for statistical assistance; and Dee Ann M. Cleary, Department of Pathology, University of Pittsburgh, for administrative support. The authors also thank The Nick Eric Wichman Foundation, Ellicott City, MD, for financial support and encouragement.
Funding Information:
Supported by The Nick Eric Wichman Foundation, Ellicott City, MD.
PY - 2004/9
Y1 - 2004/9
N2 - Hemangioblastomas (HBs) are low-grade (World Health Organization grade I/IV) central nervous system (CNS) tumors that frequently contain VHL (3p26) mutations. They occur sporadically and in von Hippel Lindau (VHL) disease. Encoded pVHL aids degradation of hypoxia-inducible factors (HIFs) in the presence of normal oxygen levels. HBs provide an in vivo view of HIF effects within a CNS tumor. Typically, HBs are cystic tumors containing a mural nodule formed by noninvasive, vacuolated stromal cells that are embedded in a network of capillaries. Nine HBs, consecutively resected from 8 patients at our institution during a recent 2-year time span, were evaluated for additional losses of tumor suppressor genes. Non-VHL microsatellites studied for loss of heterozygosity (LOH) are near tumor suppressor genes lost in gliomas, pituitary adenomas, several CNS tumors on 22q, neurofibromatosis 1, and colon carcinomas (13, 2, 2, 1, and 2 markers for each, respectively). LOH in the region of 3p21.3-3p26.3 occurred in 3 of 8 HBs informative for at least 1 marker (D3S1539, D3S2303, or D3S2373). By using 2 markers (D22S417 and D22S532) for 22q13.2, LOH was found in 5 of 8 informative HBs. All 3 HBs with allelic losses near VHL also showed LOH at 22q13.2. No consistent losses were found with markers for 1p34, LMYC, 5q21, 5q32, 9p21, 10q23, 17p13, and 19q13. LOH for the 22q13.2 region in HBs suggests that the loss of another tumor suppressor gene is involved in the pathogenesis of HBs in addition to VHL. Absence of LOH for glioma markers is consistent with the low-grade behavior of HBs.
AB - Hemangioblastomas (HBs) are low-grade (World Health Organization grade I/IV) central nervous system (CNS) tumors that frequently contain VHL (3p26) mutations. They occur sporadically and in von Hippel Lindau (VHL) disease. Encoded pVHL aids degradation of hypoxia-inducible factors (HIFs) in the presence of normal oxygen levels. HBs provide an in vivo view of HIF effects within a CNS tumor. Typically, HBs are cystic tumors containing a mural nodule formed by noninvasive, vacuolated stromal cells that are embedded in a network of capillaries. Nine HBs, consecutively resected from 8 patients at our institution during a recent 2-year time span, were evaluated for additional losses of tumor suppressor genes. Non-VHL microsatellites studied for loss of heterozygosity (LOH) are near tumor suppressor genes lost in gliomas, pituitary adenomas, several CNS tumors on 22q, neurofibromatosis 1, and colon carcinomas (13, 2, 2, 1, and 2 markers for each, respectively). LOH in the region of 3p21.3-3p26.3 occurred in 3 of 8 HBs informative for at least 1 marker (D3S1539, D3S2303, or D3S2373). By using 2 markers (D22S417 and D22S532) for 22q13.2, LOH was found in 5 of 8 informative HBs. All 3 HBs with allelic losses near VHL also showed LOH at 22q13.2. No consistent losses were found with markers for 1p34, LMYC, 5q21, 5q32, 9p21, 10q23, 17p13, and 19q13. LOH for the 22q13.2 region in HBs suggests that the loss of another tumor suppressor gene is involved in the pathogenesis of HBs in addition to VHL. Absence of LOH for glioma markers is consistent with the low-grade behavior of HBs.
KW - APC
KW - HBs
KW - HIFs
KW - LOH
KW - VEGF
KW - VHL
KW - hemangioblastoma
KW - hemangioblastomas
KW - hypoxia-inducible factors
KW - loss of heterozygosity
KW - tumor suppressor genes
KW - vascular endothelial growth factor
KW - von Hippel Lindau
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UR - http://www.scopus.com/inward/citedby.url?scp=4444383870&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2004.05.014
DO - 10.1016/j.humpath.2004.05.014
M3 - Article
C2 - 15343513
AN - SCOPUS:4444383870
SN - 0046-8177
VL - 35
SP - 1105
EP - 1111
JO - Human Pathology
JF - Human Pathology
IS - 9
ER -