Histone Demethylase Gene PHF2 Is Mutated in Gastric and Colorectal Cancers

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Histone modification gene alterations are frequent in cancers.
• PHF2, a histone demethylase gene, is a putative tumor suppressor gene (TSG) crucial for p53-mediated functions.
• Inactivating PHF2 mutations have not been previously reported in cancers.

Purpose of the Study:

• To investigate PHF2 gene mutations in colorectal cancers (CRCs) and gastric cancers (GCs).
• To determine the role of microsatellite instability (MSI-H) in PHF2 mutations.
• To assess intratumoral heterogeneity (ITH) of PHF2 mutations.

Main Methods:

• Analysis of PHF2 gene mononucleotide repeats in 124 CRCs and 79 GCs.
• Mutation screening in microsatellite stable/low MSI (MSS/MSI-L) and MSI-H cancers.
• Intratumoral heterogeneity assessment in 16 CRC cases with PHF2 mutations.

Main Results:

• Frameshift mutations in PHF2 were identified in 27.8% of MSI-H CRCs and 20.6% of MSI-H GCs.
• No PHF2 mutations were found in MSS/MSI-L cancers.
• Intratumoral heterogeneity of PHF2 mutations was observed in 12.5% of analyzed CRC cases.

Conclusions:

• The tumor suppressor gene PHF2 exhibits frameshift mutations and mutational ITH in MSI-H colorectal and gastric cancers.
• These PHF2 mutations may contribute to tumorigenesis via TSG inactivation in CRC and GC.
• PHF2 mutations represent a potential biomarker in MSI-H gastrointestinal cancers.