Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas.
The INI1/SMARCB1 protein product (INI1), a component of a transcription complex, was recently implicated in the pathogenesis of schwannomas in two members of a single family with familial schwannomatosis. Tumors were found to have both constitutional and somatic mutations of the SMARCB1 gene and showed a mosaic pattern of loss of INI1 expression by immunohistochemistry, suggesting a tumor composition of mixed null and haploinsufficient cells. To determine if this finding could be extended to all tumors arising in familial schwannomatosis, and how it compares with other multiple schwannoma syndromes [sporadic schwannomatosis and neurofibromatosis 2 (NF2)] as well as to sporadic, solitary schwannomas, we performed an immunohistochemistry analysis on 45 schwannomas from patients with multiple schwannoma syndromes and on 38 solitary, sporadic schwannomas from non-syndromic patients. A mosaic pattern of INI1 expression was seen in 93% of tumors from familial schwannomatosis patients, 55% of tumors from sporadic schwannomatosis, 83% of NF2-associated tumors and only 5% of solitary, sporadic schwannomas. These results confirm a role for INI1/SMARCB1 in multiple schwannoma syndromes and suggest that a different pathway of tumorigenesis occurs in solitary, sporadic tumors.
Patil
Sushama
S
Division of Neuropathology, Washington University School of Medicine, St Louis, MO, USA.
Perry
Arie
A
Maccollin
Mia
M
Dong
Shumin
S
Betensky
Rebecca A
RA
Yeh
Tu-Hsueh
TH
Gutmann
David H
DH
Stemmer-Rachamimov
Anat O
AO
D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D003390:Cranial Nerve Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009442:Neurilemmoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D025581:Neurofibromin 2 / Q000235:genetics; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D025581:Neurofibromin 2; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors