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Highly aggressive behavior of malignant rhabdoid tumor: a special reference to SMARCB1/INI1 gene alterations using molecular genetic analysis including quantitative real-time PCR

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Abstract

Purpose

SMARCB1/INI1, which negatively regulates cell cycle progression from G0/G1 into the S-phase via the p16INK4a-RB-E2F pathway, has been reported to be inactivated homozygously by deletion and/or mutations in malignant rhabdoid tumor (MRT). In the current study, we investigated the alteration of the SMARCB1/INI1 gene using simple methods, and its gene product at the protein level. Moreover, we investigated the status of hyperphosphorylation in RB protein, known as a key cell cycle molecule.

Methods

Three cell lines and 11 formalin-fixed, paraffin-embedded specimens of MRT were investigated. SMARCB1/INI1 gene alteration was analyzed with simple methods as a quantitative real-time PCR and direct sequencing method. Furthermore, SMARCB1/INI1 and RB protein were immunohistochemically evaluated.

Results

In 12 of 14 cases, we detected genetic alterations comprised of nine (including three cell lines) homozygous deletions and three mutations, which can induce abnormal expression of gene products. At the protein level, SMARCB1/INI1 immunohistochemical expressions were not detected in any cases. Twelve out of 14 cases showed high-level (+5) expression of tRB (both hyperphosphorylated and underphosphorylated RB), combined with low-level (+1) expression of uRB (underphosphorylated RB), indicating a high rate of hyperphosphorylation.

Conclusions

We could analyze the SMARCB1/INI1 gene alteration with simple methods, and SMARCB1/INI1 gene alteration was found in 12 of 14 cases. Especially, quantitative real-time PCR was a convenient and accurate method. In addition, a high rate of hyperphosphorylation of RB gene was recognized. These results suggest that the clinically aggressive character of MRT is caused by the inactivation of the SMARCB1/INI1 gene.

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Abbreviations

MRT:

Malignant rhabdoid tumor

EMRT:

Extrarenal malignant rhabdoid tumor

MRTK:

Malignant rhabdoid tumor of the kidney

tRB:

Both hyperphosphorylated and underphosphorylated RB

uRB:

Underphosphorylated RB

Ct:

Threshold cycle numbers

GDR:

Gene dosage ratio

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research (C) (no. 18590332) from the Japan Society for the Promotion of Science, Tokyo, Japan. English used in this manuscript was revised by KN International (http://www.kninter.com/).

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Authors and Affiliations

  1. Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan

    Kenichi Kohashi, Yoshinao Oda, Hidetaka Yamamoto, Sadafumi Tamiya, Teiyu Izumi & Masazumi Tsuneyoshi

  2. Department of Pediatrics, Shiga University of Medical Science, Tsukinowa, Ohtsu, Shiga, 520-2192, Japan

    Shigeru Ohta

  3. Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan

    Tomoaki Taguchi & Sachiyo Suita

Authors
  1. Kenichi Kohashi
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  2. Yoshinao Oda
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  3. Hidetaka Yamamoto
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  4. Sadafumi Tamiya
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  5. Teiyu Izumi
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  9. Masazumi Tsuneyoshi
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Correspondence to Yoshinao Oda or Masazumi Tsuneyoshi.

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Kohashi, K., Oda, Y., Yamamoto, H. et al. Highly aggressive behavior of malignant rhabdoid tumor: a special reference to SMARCB1/INI1 gene alterations using molecular genetic analysis including quantitative real-time PCR. J Cancer Res Clin Oncol 133, 817–824 (2007). https://doi.org/10.1007/s00432-007-0223-z

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  • DOI: https://doi.org/10.1007/s00432-007-0223-z

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