Putative Tumor Suppressor Genes EGR1 and BRSK1 Are Mutated in Gastric and Colorectal Cancers.

OBJECTIVE:The transcription factor-encoding EGR1 and the kinase-encoding BRSK1 are considered putative tumor suppressor genes (TSGs). However, EGR1 and BRSK1 mutations that could inactivate their functions are not reported in colorectal (CRC) and gastric (GC) cancers. METHODS:There are mononucleotide repeats in EGR1 and BRSK1, which could be mutated in cancers with defects in mismatch repair, resulting in microsatellite instability (MSI). We analyzed 124 CRCs and 79 GCs for mutations and their intratumoral heterogeneities (ITHs). RESULTS:Twenty-one out of 79 CRCs (26.6%) and 5 out of 34 GCs (14.7%) carrying high MSI (MSI-H) exhibited frameshift mutations. However, we found no such mutations in cancers with microsatellite stability. In addition, we studied ITH for these mutations in 16 cases of CRCs and observed that EGR1 and BRSK1 mutations exhibited ITH in 3 (18.8%) and 2 (12.5%) cases, respectively. CONCLUSION:Our data in this study reveal that the TSG genes EGR1 and BRSK1 carry mutational ITH as well as frameshift mutations in MSI-H CRC and GC, which together may be features of GC and CRC with MSI-H. These results suggest that frameshift mutations of EGR1 and BRSK1 might play a role in tumorigenesis through TSG inactivation in CRC and GC.

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