PTEN and colorectal carcinoma: We were intrigued by IRS2, as its downstream signaling pathway has previously been associated with BM development via PTEN loss.19 Furthermore, the three key altered genes - IRS2, CDK8, and FLT3 - are all located on chromosome 13q, a region commonly gained in CRC with a prevalence of up to 85%.20 A recent study analyzing 124 primary CRCs refined the minimal copy region on 13q and identified IRS2 as the only whole gene within it, supporting its role as a potential driver oncogene.9