Intact INI1 gene region with paradoxical loss of protein expression in AT/RT: Implications for a possible novel mechanism associated with absence of INI1 protein immunoreactivity

Chan Yen Tsai, Tai-Tong Wong, Yu Hsiu Lee, Meng En Chao, Shih Chieh Lin, Da Jung Liu, Muh Lii Liang, Hsei Wei Wang, Donald Ming-Tak Ho

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26 引文 斯高帕斯(Scopus)

摘要

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system tumor often misdiagnosed as some other type of pediatric embryonal tumor, such as medulloblastoma (MB). Distinguishing AT/RT from primitive neuroectodermal tumor/MB is of clinical significance, as the reported survival rate of patients with AT/RT is much lower than that of patients with average-risk primitive neuroectodermal tumor/MB. The diagnosis of AT/RT currently relies primarily on the morphologic assessment and immunostaining of a few known markers, such as the lack of INI1 protein expression. Immunohistochemical staining of INI1 is considered very sensitive and is highly specific for the detection of INI1 genetic defects. Genetic studies have shown that deletion or mutation of the INI1 gene, which is located on 22q11.2, occurs in AT/RT lesions. During our gene expression microarray analysis, we unexpectedly found a subgroup of AT/RT patients still expressing INI1 mRNA, even though INI1 proteins were negative by immunohistochemistry in those cases. Direct DNA sequencing showed no INI1 sequence alternation in 3 of 4 AT/RTs. Point mutation was found in only 1 allele of the fourth case, which would result in a frameshift mutation and generate a new INI1 protein with an extra 100-aa tail. Global array comparative genomic hybridization analysis confirmed no aberration around the INI1 gene at 22q11.2. It also extended our knowledge on the chromosomal aberration situations in our series. This study reveals that a novel yet unidentified posttranscriptional regulatory mechanism(s) for INI1 protein synthesis exists in AT/RT tumor cells.

原文英語
頁(從 - 到)128-133
頁數6
期刊American Journal of Surgical Pathology
36
發行號1
DOIs
出版狀態已發佈 - 一月 1 2012
對外發佈

ASJC Scopus subject areas

  • 解剖學
  • 手術
  • 病理學與法醫學

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