STK10 missense mutations associated with anti-apoptotic function

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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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-κ;B 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.

Original languageEnglish
Pages (from-to)1542-1548
Number of pages7
JournalOncology reports
Volume30
Issue number4
DOIs
Publication statusPublished - Oct 2013
Externally publishedYes

Keywords

  • Apoptosis
  • NF-κ;B
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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