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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)128-133
Number of pages6
JournalAmerican Journal of Surgical Pathology
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 1 2012
Externally publishedYes

Fingerprint

Medulloblastoma
Genes
Proteins
Primitive Neuroectodermal Tumors
Central Nervous System Neoplasms
Frameshift Mutation
Comparative Genomic Hybridization
Sequence Deletion
Microarray Analysis
Typical Teratoid Rhabdoid Tumor
Atypical Teratoid Tumor
Diagnostic Errors
DNA Sequence Analysis
Point Mutation
Chromosome Aberrations
Neoplasms
Survival Rate
Immunohistochemistry
Alleles
Pediatrics

Keywords

  • array CGH
  • atypical teratoid/rhabdoid tumor
  • INI1
  • medulloblastoma
  • pediatric brain tumor

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

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

In: American Journal of Surgical Pathology, Vol. 36, No. 1, 01.01.2012, p. 128-133.

Research output: Contribution to journalArticle

Tsai, Chan Yen ; Wong, Tai-Tong ; Lee, Yu Hsiu ; Chao, Meng En ; Lin, Shih Chieh ; Liu, Da Jung ; Liang, Muh Lii ; Wang, Hsei Wei ; Ming-Tak Ho, Donald. / 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. In: American Journal of Surgical Pathology. 2012 ; Vol. 36, No. 1. pp. 128-133.
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