TY - JOUR
T1 - R132C IDH1 mutations are found in spindle cell hemangiomas and not in other vascular tumors or malformations
AU - Kurek, Kyle C.
AU - Pansuriya, Twinkal C.
AU - Van Ruler, Maayke A.J.H.
AU - Van Den Akker, Brendy
AU - Luks, Valerie L.
AU - Verbeke, Sofie L.J.
AU - Kozakewich, Harry P.
AU - Sciot, Raf
AU - Lev, Dina
AU - Lazar, Alexander J.
AU - Fletcher, Christopher D.M.
AU - Bovée, Judith V.M.G.
N1 - Funding Information:
Supported in part by the Netherlands Organization for Scientific Research ( 917-67-315 to J.V.M.G.B.).
PY - 2013/5
Y1 - 2013/5
N2 - Spindle cell hemangioma (SCH) is a rare, benign vascular tumor of the dermis and subcutis. The lesions can be multifocal and are overrepresented in Maffucci syndrome, in which patients also have multiple enchondromas. Somatic mosaic R132C IDH1 hotspot mutations were recently identified in Maffucci syndrome. We evaluated the presence of mutations in solitary and multiple SCHs in patients without multiple enchondromas and tested a range of other vascular lesions that enter into the differential diagnosis. The R132C IDH1 mutation was identified by hydrolysis probes assay and confirmed by Sanger sequencing in 18 of 28 (64%) SCHs; of the 10 negative cases, 2 harbored a mutation in IDH2 (R172T and R172M) by Sanger sequencing. None of 154 other vascular malformations and tumors harbored an IDH1 R132C mutation, and R132H IDH1 mutations were absent in all 182 cases. All 16 SCHs examined by immunohistochemistry were negative for expression of HIF-1α. In conclusion, 20 of 28 (71%) SCHs harbored mutations in exon 4 of IDH1 or IDH2. Given that mutations were absent in 154 other vascular lesions, the mutation seems to be highly specific for SCH. The mutation does not induce expression of HIF-1α in SCH, and therefore the exact mechanism by which mutations in IDH1 or IDH2 lead to vascular tumorigenesis remains to be established.
AB - Spindle cell hemangioma (SCH) is a rare, benign vascular tumor of the dermis and subcutis. The lesions can be multifocal and are overrepresented in Maffucci syndrome, in which patients also have multiple enchondromas. Somatic mosaic R132C IDH1 hotspot mutations were recently identified in Maffucci syndrome. We evaluated the presence of mutations in solitary and multiple SCHs in patients without multiple enchondromas and tested a range of other vascular lesions that enter into the differential diagnosis. The R132C IDH1 mutation was identified by hydrolysis probes assay and confirmed by Sanger sequencing in 18 of 28 (64%) SCHs; of the 10 negative cases, 2 harbored a mutation in IDH2 (R172T and R172M) by Sanger sequencing. None of 154 other vascular malformations and tumors harbored an IDH1 R132C mutation, and R132H IDH1 mutations were absent in all 182 cases. All 16 SCHs examined by immunohistochemistry were negative for expression of HIF-1α. In conclusion, 20 of 28 (71%) SCHs harbored mutations in exon 4 of IDH1 or IDH2. Given that mutations were absent in 154 other vascular lesions, the mutation seems to be highly specific for SCH. The mutation does not induce expression of HIF-1α in SCH, and therefore the exact mechanism by which mutations in IDH1 or IDH2 lead to vascular tumorigenesis remains to be established.
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U2 - 10.1016/j.ajpath.2013.01.012
DO - 10.1016/j.ajpath.2013.01.012
M3 - Article
C2 - 23485734
AN - SCOPUS:84876526224
SN - 0002-9440
VL - 182
SP - 1494
EP - 1500
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -