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.


CONCLUSIONS
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.
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Eun Ji
EJ
Choi
Nam Jin
NJ
Yoo
Min Sung
MS
Kim
Chang Hyeok
CH
An
Sug Hyung
SH
Lee
D015179:Colorectal Neoplasms / Q000235:genetics*; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D016368:Frameshift Mutation; D018740:Genetic Heterogeneity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D053842:Microsatellite Instability; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D047908:Intracellular Signaling Peptides and Proteins; C523084:BRSK1 protein, human; D017346:Protein Serine-Threonine Kinases