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Frameshift Mutations of AKAP9 Gene in Gastric and Colorectal Cancers with High Microsatellite Instability

Yun Sol Jo1, Min Sung Kim1, Nam Jin Yoo1

  • 1Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.

Pathology Oncology Research : POR
|January 21, 2016
PubMed

Insights

A-kinase-anchoring protein 9 (AKAP9) frameshift mutations are common in microsatellite instability-high (MSI-H) gastric and colorectal cancers. Intratumoral heterogeneity of these AKAP9 mutations was also observed, suggesting a need for regional mutation analysis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • A-kinase-anchoring protein 9 (AKAP9) is crucial for cell cycle regulation and maintaining cell membrane integrity, with its alterations linked to tumorigenesis.
  • Somatic mutations in AKAP9 have been identified in various cancers, but its mutation profile in relation to microsatellite instability (MSI) remains largely unexplored.
  • Mononucleotide repeats within the AKAP9 gene coding sequences suggest it as a potential target for mutations in MSI-high cancers.

Purpose of the Study:

  • To investigate the mutation status of the AKAP9 gene in gastric cancer (GC) and colorectal cancer (CRC) concerning microsatellite instability (MSI).
  • To determine the frequency of AKAP9 frameshift mutations in MSI-high (MSI-H) versus microsatellite stable/low MSI (MSS/MSI-L) GC and CRC.
  • To assess the intratumoral heterogeneity (ITH) of AKAP9 frameshift mutations in CRC.

Main Methods:

  • Analysis of AKAP9 gene mutations in 79 GCs and 124 CRCs using single-strand conformation polymorphism (SSCP) and DNA sequencing.
  • Categorization of samples into MSI-H and MSS/MSI-L groups.
  • Evaluation of regional intratumoral heterogeneity (ITH) of AKAP9 mutations in a subset of 16 CRCs.

Main Results:

  • AKAP9 frameshift mutations were detected in 11.7% of GCs and 17.7% of CRCs, exclusively in MSI-H cases (24/113).
  • No AKAP9 mutations were found in MSS/MSI-L cancers (0/90), indicating a significant association with MSI-H status (p < 0.001).
  • Regional ITH of AKAP9 frameshift mutations was observed in 31.3% (5/16) of the analyzed CRCs.

Conclusions:

  • The AKAP9 gene is a target for somatic frameshift mutations and exhibits mutational ITH in MSI-H gastric and colorectal cancers.
  • These findings suggest that AKAP9 mutations and their heterogeneity are characteristic features of MSI-H GC and CRC.
  • Regional mutation analysis is recommended for accurate assessment of mutation status in these tumors to account for ITH.
Keywords:
AKAP9CancerFameshift mutationMicrosatellite instability

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