Mutational analysis of INI1 in sporadic human brain tumors

Weber, M.; Stockhammer, Florian; Schmitz, Ulrike; Deimling, Andreas von

doi:10.1007/s004010000316

Cited by 33 publications

(16 citation statements)

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“…The diagnoses in these cases are supported by detection of chromosome 22q11.2 deletions and loss of INI1 protein expression in all 3 and a mutation in the INI1 gene in one. Although not completely specific, identification of INI1 inactivation is of considerable diagnostic value as alterations of this gene appear to be restricted to a subset of CNS tumors (10,13,19,21). In addition, we found, recently, that only 13% of composite extrarenal rhabdoid tumors, other tumor types that secondarily become rhabdoid, showed 22q11.2 deletions and, in those cases, the NF2 region was also deleted (9).…”

Section: Discussionmentioning

confidence: 88%

Chromosome 22q Deletions in Atypical Teratoid/Rhabdoid Tumors in Adults

et al. 2006

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Atypical teratoid/rhabdoid tumors (AT/RTs) are rare, malignant brain tumors that usually occur in the posterior fossa. Both AT/RT and the analogous tumor outside the brain, malignant rhabdoid tumor, share a polyphenotypic immunoprofile and frequent 22q deletions with inactivation of the IN11/hSNF5 gene. Reports, so far, indicate that AT/RTs occur almost exclusively in children, most of whom are 5-years-old or less. The rarity of the tumor and the polyphenotypic immunoprofile, characterized by antigen expression that is often patchy, make diagnosis in adults difficult and controversial. We describe three AT/RTs in adults in which the diagnoses were supported by detection of 22q11.2 deletions, INI1 mutation and/or loss of INI1 protein expression. Two patients were female, ages 20 and 31 and one was male, age 45. Two tumors occurred in the sella or sellar region and one in the cerebellum. In all cases, fluorescence in situ hybridization with probes to the BCR (22q11.2) and NF2 (22q12) regions of chromosome 22 revealed single copy deletions of BCR with normal dosages of NF2 and, in all cases, immunohistochemistry demonstrated loss of INI1 protein expression. In one case, a single base pair deletion was detected in the INI1/hSNF5 gene. These molecular findings confirm the occurrence of AT/RTs in adults. Although rare, AT/RT should be considered in the differential diagnosis of poorly differentiated intracranial tumors in adults.

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Section: Discussionmentioning

confidence: 88%

Chromosome 22q Deletions in Atypical Teratoid/Rhabdoid Tumors in Adults

et al. 2006

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“…Subsequently, it was found to act as a true tumor suppressor in rhabdoid tumors of infancy and young childhood, including those with constitutional mutations and the rhabdoid predisposition syndrome (6,7). A multitude of other tumor types have been examined for mutations in SMARCB1 with variable results, including two studies of presumably sporadic schwannomas that failed to detect alterations (8,9). SMARCB1 lies within the familial schwannomatosis candidate region, and constitutional alterations with paired somatic mutation or LOH have been described in six schwannomatosis kindreds and several sporadically affected individuals (10)(11)(12).…”

Section: Boyd a Mj Smith A L Kluwe B A Balogh A M Maccollinmentioning

confidence: 99%

Molecular Identification of the Schwannomatosis Locus

MacCollin¹,

Plotkin²

2008

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In 2007, mutations in the SMARCB1 tumor suppressor (also known as INI1 and hSNF5), which lies in the familial schwannomatosis candidate region, were detected on a somatic and constitutional level in a single kindred with schwannomatosis. We have completed our study of 19 schwannomatosis kindreds who were unrelated to the best of the study participants' knowledge. Overall, we identified potentially causative constitutional alterations in 13 families, including 2 missense mutations (in 3 families), 4 splice site mutations, 2 additional mutations thought to be splice site mutations, and 4 changes of presumed pathogenicity in exon 9 (c.1240C>T). We compared haplotypes of the retained (affected) allele in tumorsfrom families with recurrent mutations in SMARCB1. Differing haplotypes were seen in 4 families with the c.1240C>T mutation in exon 9, which argues against a common ancestor. In contrast, a similar haplotype was seen in 2 families for c.158G>T mutation in exon 2 which suggests a common ancestor. 15. SUBJECT TERMS None provided. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON

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“…SMARCB1 has been extensively studied as a critical player in cell state regulation. One of its well-known roles is as a tumor suppressor gene [12], and it is genetically mutated/inactivated over a wide spectrum of cancers, including rhabdoid, brain, kidney, and other tissue tumors [13][14][15]. One of the SMARCB1-related oncogenic pathways is cell cycle regulation.…”

Section: Introductionmentioning

confidence: 99%

SMARCB1 Acts as a Quiescent Gatekeeper for Cell Cycle and Immune Response in Human Cells

Choi

Kim

You

2020

IJMS

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Switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, one of the adenosine triphosphate (ATP)-dependent chromatin remodeler complexes. The unique role of SMARCB1 has been reported in various cellular contexts. Here, we focused on the general role of the ubiquitous expression of SMARCB1 in a normal cell state. We selected ARPE19 (human primary retinal pigment epithelium) and IMR90 (from human fetal lung fibroblasts) cell lines as they have completely different contexts. Furthermore, although these cell lines have been immortalized, they are relatively close to normal human cells. The loss of SMARCB1 in ARPE19 and IMR90 cells reduced cell cycle progression via the upregulation of P21. Transcriptome analysis followed by SMARCB1 knockdown in both cell lines revealed that SMARCB1 was not only involved in cell maintenance but also conferred immunomodulation. Of note, SMARCB1 bound to interleukin (IL) 6 promoter in a steady state and dissociated in an active immune response state, suggesting that SMARCB1 was a direct repressor of IL6, which was further confirmed via loss- and gain-of-function studies. Taken together, we demonstrated that SMARCB1 is a critical gatekeeper molecule of the cell cycle and immune response.

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Mutational analysis of INI1 in sporadic human brain tumors

Cited by 33 publications

References 0 publications

Chromosome 22q Deletions in Atypical Teratoid/Rhabdoid Tumors in Adults

Chromosome 22q Deletions in Atypical Teratoid/Rhabdoid Tumors in Adults

Molecular Identification of the Schwannomatosis Locus

SMARCB1 Acts as a Quiescent Gatekeeper for Cell Cycle and Immune Response in Human Cells

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