Expression and Mutation Alterations of ZMYM4 Gene in Gastric and Colonic Cancers

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• ZMYM4, a zinc finger protein, has known roles in cell shape and death.
• Its specific involvement in gastrointestinal cancers, particularly those with high microsatellite instability (MSI-H), requires further investigation.

Purpose of the Study:

• To investigate the frequency and impact of ZMYM4 gene alterations in gastric cancer (GC) and colonic cancer (CC) with MSI-H.
• To assess the relationship between ZMYM4 mutations, intratumoral heterogeneity, and gene expression levels in these cancers.

Main Methods:

• Analysis of mononucleotide repeat sites within the ZMYM4 coding sequence in MSI-H and microsatellite-stable GC and CC samples.
• Assessment of ZMYM4 frameshift mutations and intratumoral heterogeneity.
• Quantification of ZMYM4 gene expression in relation to mutation status.

Main Results:

• ZMYM4 frameshift mutations were identified in 21.9% of MSI-H GCs and 20.4% of MSI-H CCs, with no significant difference between cancer types.
• No mutations were found in microsatellite-stable samples.
• Intratumoral heterogeneity of ZMYM4 mutations was observed in 37.5% of MSI-H CCs.
• Significantly lower ZMYM4 expression was noted in mutated cases compared to non-mutated cases in both GC and CC with MSI-H.

Conclusions:

• ZMYM4 is frequently altered in MSI-H gastric and colonic cancers through frameshift mutations and loss of expression.
• Mutational intratumoral heterogeneity of ZMYM4 is present in MSI-H colonic cancer.
• These findings suggest a significant role for ZMYM4 alterations in the development or progression of MSI-H gastrointestinal cancers.