STK10 missense mutations associated with anti-apoptotic function

Fukumura,Kazutaka; Yamashita,Yoshihiro; Kawazu,Masahito; Sai,Eirin; Fujiwara,Shin-Ichiro; Nakamura,Naoya; Takeuchi,Kengo; Ando,Mizuo; Miyazono,Kohei; Ueno,Toshihide; Ozawa,Keiya; Mano,Hiroyuki

doi:10.3892/or.2013.2605

October 2013 Volume 30 Issue 4

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October 2013 Volume 30 Issue 4

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Article

STK10 missense mutations associated with anti-apoptotic function

Authors:
- Kazutaka Fukumura
- Yoshihiro Yamashita
- Masahito Kawazu
- Eirin Sai
- Shin-Ichiro Fujiwara
- Naoya Nakamura
- Kengo Takeuchi
- Mizuo Ando
- Kohei Miyazono
- Toshihide Ueno
- Keiya Ozawa
- Hiroyuki Mano
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Affiliations: Department of Medical Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan, Division of Functional Genomics, Jichi Medical University, Tochigi 329-0498, Japan, Department of Hematology, Jichi Medical University, Tochigi 329-0498, Japan, Department of Pathology, Tokai University School of Medicine, Kanagawa 259-1193, Japan, Pathology Project for Molecular Targets, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan, Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan, Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Pages: 1542-1548
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Published online on: July 9, 2013

https://doi.org/10.3892/or.2013.2605
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Abstract

Peripheral T-cell lymphoma (PTCL) is an aggressive lymphoma with a 5-year overall survival rate of <30%. To identify carcinogenesis-related genes in PTCL, we conducted high-throughput resequencing of target-captured cDNA in a PTCL specimen, revealing a total of 19 missense mutations among 18 independent genes. One of such substitutions, c.2201G>A in STK10 cDNA, replaces an arginine residue to a histidine (R634H) in the encoded protein. Of note, while wild-type STK10 suppresses NF-κB activity and potentiates dexamethasone-induced apoptosis, the R634H change significantly decreases such pro-apoptotic activity. This c.2201G>A change of STK10 was also identified in another PTCL specimen, but now registered as a single nucleotide polymorphism in the latest dbSNP database. Furthermore, other somatic mutations of STK10 have been reported, and we now reveal that some of them (L85P and K277E) have more profound anti-apoptotic effects compared to R634H. These results suggest that STK10 functions as a tumor suppressor gene, and that dysfunction of STK10 activity either through polymorphism or somatic mutations may confer anti-apoptotic effects contributing to carcinogenesis.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

STK10 missense mutations associated with anti-apoptotic function

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