INI1 mutations in meningiomas at a potential hotspot in exon 9

Abstract

SummaryRhabdoid tumours have been shown to carry somatic mutations in the INI1 (SMARCB1/hSNF5) gene. A considerable fraction of these tumours exhibit allelic losses on chromosome 22. Allelic loss on 22q also is characteristic for meningiomas, however most of these alterations are considered to be associated with mutations of the NF2 gene. We examined a series of 126 meningiomas for alterations in the INI1 gene. Four identical somatic mutations in exon 9 were detected resulting in an exchange of Arg to His in position 377 of INI1. Our observations were reproduced both by using DNA from a new round of extraction and by employing overlapping primers. This mutational hotspot therefore appears to be an important target in the formation of a fraction of meningiomas. In addition, 4 novel polymorphisms of INI1 were characterized. Our data indicate that the INI1 is a second tumour suppressor gene on chromosome 22 that may be important for the genesis of meningiomas.

INI1 expression is retained in composite rhabdoid tumors, including rhabdoid meningiomas

“…The latter is particularly relevant given that INI1 mutations have been recently reported in a small subset of meningiomas. 37,38 Given that this gene was not inactivated in our cases, it is likely that the primary target in the subset of rhabdoid meningiomas with 22q deletion is the more telomeric NF2 gene on 22q12, just as it is in classic meningiomas.…”

HLTF gene silencing in human colon cancer

“…he SWI͞SNF family of genes, which encode a group of chromatin remodeling engines, have recently been implicated as playing a role in cancer (1)(2)(3). Membership in the SWI͞SNF superfamily is defined by a structure of seven DNAdependent ATPase motifs that is conserved in organisms from yeast to humans, and as members of multiprotein complexes SWI͞SNF proteins use the energy of ATP hydrolysis to alter nucleosome position or spacing (4,5).…”

“…Human hSNF5͞INI1 gene was found to be inactivated frequently in pediatric malignant rhabdoid tumors (3), meningiomas (2), and lymphoid tumors (14). BRG1 inactivation mutations have been reported in human prostate, breast, pancreas, and lung tumor cell lines (15), whereas mutations of RAD54b were reported in human primary lymphoma and colon cancer (1), suggesting that SWI͞SNF genes can function as tumor suppressor genes.…”

Roles of SWI/SNF Complex Genes in Breast Cancer

“…Furthermore, loss of Ini1 was redundant with loss of Rb function in the formation of pituitary tumors in Rb heterozygous mice and gave rise to the formation of large, atypical Rb(+/-) tumor cells lacking adrenocorticotropic hormone expression, confirming in vivo the relationship between Rb and Ini1 in tumor suppression [74]. Mutations and alterations of SNF5 were also reported in familial schwannomatosis and other cancer types [75][76][77][78][79][80][81][82][83][84]. Germ line mutations of SNF5 were detected in brain tumors and rhabdoid tumors, suggesting its link with familial cancers [85][86][87][88].…”