Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas

Sushama Patil, Arie Perry, Mia MacCollin, Shumin Dong, Rebecca Betensky, Tu Hsueh Yeh, David H. Gutmann, Anat O. Stemmer-Rachamimov

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)517-519
Number of pages3
JournalBrain Pathology
Volume18
Issue number4
DOIs
StatePublished - Oct 1 2008

Fingerprint

Neurilemmoma
Neoplasms
Neurofibromatosis 2
Immunohistochemistry
Null Lymphocytes
Carcinogenesis
Schwannomatosis
Mutation
Genes

Keywords

  • Expression
  • INI1
  • NF2
  • Schwannoma
  • Schwannomatosis
  • SMARCB1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas. / Patil, Sushama; Perry, Arie; MacCollin, Mia; Dong, Shumin; Betensky, Rebecca; Yeh, Tu Hsueh; Gutmann, David H.; Stemmer-Rachamimov, Anat O.

In: Brain Pathology, Vol. 18, No. 4, 01.10.2008, p. 517-519.

Research output: Contribution to journalArticle

Patil, Sushama ; Perry, Arie ; MacCollin, Mia ; Dong, Shumin ; Betensky, Rebecca ; Yeh, Tu Hsueh ; Gutmann, David H. ; Stemmer-Rachamimov, Anat O. / Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas. In: Brain Pathology. 2008 ; Vol. 18, No. 4. pp. 517-519.
@article{343b2fdf51814e9d8f2d42e6f3e220f9,
title = "Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas",
abstract = "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.",
keywords = "Expression, INI1, NF2, Schwannoma, Schwannomatosis, SMARCB1",
author = "Sushama Patil and Arie Perry and Mia MacCollin and Shumin Dong and Rebecca Betensky and Yeh, {Tu Hsueh} and Gutmann, {David H.} and Stemmer-Rachamimov, {Anat O.}",
year = "2008",
month = "10",
day = "1",
doi = "10.1111/j.1750-3639.2008.00155.x",
language = "English (US)",
volume = "18",
pages = "517--519",
journal = "Brain Pathology",
issn = "1015-6305",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas

AU - Patil, Sushama

AU - Perry, Arie

AU - MacCollin, Mia

AU - Dong, Shumin

AU - Betensky, Rebecca

AU - Yeh, Tu Hsueh

AU - Gutmann, David H.

AU - Stemmer-Rachamimov, Anat O.

PY - 2008/10/1

Y1 - 2008/10/1

N2 - 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.

AB - 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.

KW - Expression

KW - INI1

KW - NF2

KW - Schwannoma

KW - Schwannomatosis

KW - SMARCB1

UR - http://www.scopus.com/inward/record.url?scp=51249115377&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=51249115377&partnerID=8YFLogxK

U2 - 10.1111/j.1750-3639.2008.00155.x

DO - 10.1111/j.1750-3639.2008.00155.x

M3 - Article

VL - 18

SP - 517

EP - 519

JO - Brain Pathology

JF - Brain Pathology

SN - 1015-6305

IS - 4

ER -