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

Hyun Ji Son1, Yun Sol Jo1, Min Sung Kim1

  • 1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Pathology, Research and Practice
|November 28, 2018
PubMed

Insights

Tumor suppressor genes DAB2IP and DAB2 were investigated for mutations in gastric and colorectal cancers. Frameshift mutations in DAB2IP were found in high microsatellite instability cancers, suggesting a role in tumorigenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • DAB2 and DAB2IP are scaffold proteins with potential tumor suppressor gene (TSG) functions.
  • Previous research indicated promoter hypermethylation inactivates DAB2 and DAB2IP in cancers.
  • Mutational alterations of these genes in cancer remain largely uncharacterized.

Purpose of the Study:

  • To investigate the presence and frequency of mutations in DAB2 and DAB2IP genes in gastric cancers (GCs) and colorectal cancers (CRCs).
  • To explore the potential role of these mutations in cancer development, particularly in tumors with high microsatellite instability (MSI-H).

Main Methods:

  • DNA sequencing was employed to analyze tumor tissues from GCs and CRCs.
  • Analysis focused on identifying mutations within the coding sequences of DAB2 and DAB2IP, especially in regions with mononucleotide repeats.
  • Microsatellite instability (MSI) status and protein expression levels were assessed.

Main Results:

  • Frameshift mutations in DAB2IP were identified in 23.5% of MSI-H GCs and 20.0% of MSI-H CRCs.
  • DAB2 frameshift mutations were found in 2.5% of MSI-H CRCs.
  • These mutations were absent in microsatellite-stable (MSS) cancers.
  • Intratumoral heterogeneity (ITH) of DAB2IP mutations was observed in 43.8% of CRCs.
  • Loss of DAB2IP protein expression occurred in approximately 20% of GCs and CRCs, independent of mutation status.

Conclusions:

  • The tumor suppressor gene DAB2IP is subject to frameshift mutations, intratumoral heterogeneity, and expression loss in gastric and colorectal cancers.
  • These alterations, particularly in MSI-H tumors, may contribute to tumorigenesis by reducing DAB2IP's tumor-inhibiting functions.
Keywords:
DAB2DAB2IPFrameshift mutationGI cancerMicrosatellite instabilityTumor suppressor gene

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