DAB2IP with tumor-inhibiting activities exhibits frameshift mutations in gastrointestinal cancers

Hyun Ji Son, Yun Sol Jo, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

A scaffold protein DAB2 and its interaction partner DAB2IP have putative tumor suppressor gene (TSG) functions. Previous studies identified that both DAB2 and DAB2IP genes were inactivated by promoter hypermethylation in human cancers, but their mutational alterations in cancers remain largely unknown. The aim of our study was to find whether DAB2 and DAB2IP were mutated in gastric (GCs) and colorectal cancers (CRCs) by DNA sequencing. Both DAB2 and DAB2IP have mononucleotide repeats in their coding sequence that could be mutation targets in high microsatellite instability (MSI-H) cancers. We analyzed GC and CRC tissues and found that 8 of 34 GCs (23.5%) and 15 of 79 CRCs (20.0%) with MSI-H harbored DAB2IP frameshift mutations. DAB2 frameshift mutations were found in 2 of 79 CRCs (2.5%) with MSI-H. These mutations were not detected in microsatellite stable (MSS) cancers. We also found intratumoral heterogeneity (ITH) of DAB2IP frameshift mutations in 7 of 16 CRCs (43.8%). Loss of DAB2IP protein expression was found in approximately 20% of GCs and CRCs irrespective of MSI and DAB2IP frameshift mutation status. Our study shows that the TSG DAB2IP harbored frameshift mutations and ITH as well as expression loss. Together these tumor alterations might play a role in tumorigenesis of GC and CRC with MSI-H by down-regulating the tumor-inhibiting activities of DAB2IP.

Original languageEnglish
Pages (from-to)2075-2080
Number of pages6
JournalPathology Research and Practice
Volume214
Issue number12
DOIs
StatePublished - Dec 2018

Bibliographical note

Funding Information:
This study was supported by grants from National Research Foundation of Korea ( 2012R1A5A2047939 ).

Publisher Copyright:
© 2018 Elsevier GmbH

Keywords

  • DAB2
  • DAB2IP
  • Frameshift mutation
  • GI cancer
  • Microsatellite instability
  • Tumor suppressor gene

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