Amplification of MPZL1/PZR gene in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality worldwide. It is noted that metastasis is a fundamental biological behavior of HCC and the main cause of treatment failure. The identification of somatic alterations and their specific inhibitors may contribute to reduce side effects and prolong patient survival in HCC. Chromosomal copy number alterations (CNAs) are important subclasses of somatic mutations and can be used as an effective method of identifying driver genes with causal roles in carcinogenesis. Jia et al. identified a novel recurrent focal amplicon, 1q24.1-24.2, targets the MPZL1 gene in HCC. They also found that MPZL1 may recruit the SHP-2 and subsequently activate/phosphorylate Src kinase at Tyr426, promoting phosphorylation of cortactin and migration of HCC cells. It is noted that phosphorylation of Tyr416 in the activation loop of the kinase domain up-regulates enzyme activity of Src. In addition, the active state of c-Src, p-Tyr416-c-Src, is an independent prognostic marker of poor patient survival in HCC. Therefore, c-Src signaling may be a druggable target and c-Src targeted therapy may improve patient outcome in this specific subtype of HCC patient with a gain of the recurrent focal amplicon, 1q24.1-24.2.