Prognostic Significance of CHEK2 Mutation in Progression of Breast Cancer

Narges Ansari, MD; Saeid Shahrabi, PhD; Abbas Khosravi, PhD; Reza Shirzad, Msc; Hadi Rezaeean, Msc


Lab Med. 2019;50(3):e36-e41. 

In This Article

Discussion and Future Perspectives

BC is one of the most common cancers in various societies. BC diagnosis in advanced stages of disease results in lack of patient response to treatment and increases patient mortality.[54] Mutations of genes that encode the cell signaling pathway have been implicated in the incidence of BC.[55] However, evidence from recent studies[56] suggests that mutations in CHEK2 are of high importance because of the indirect role of this factor in vital cellular processes such as cell cycle and apoptosis. Among these mutations, c.1100delC and I157T seem to be involved in metastasis of BC cells to other parts of the body, which highlights the clinical importance of these 2 mutations in response to treatment.

Research[57] has indicated that c.1100delC mutation plays a role in predisposition of males to BC; BC in males is a rare phenomenon and also causes metastasis of breast tumor cells to other parts of the body. However, I157T mutation also plays a role in metastatic ductal breast carcinoma, which is a variant of BC. Therefore, the presence of c.1100delC and I157T mutations in patients can be associated with poor prognosis and reduced survival of patients.[49] Despite this, the occurrence of mutations in the kinase domain of CHEK2 can affect cell susceptibility to chemotherapy drugs and the induction of apoptosis in those cells (Table 2).

Thus, identifying mutation in CHEK2 domains can be effective in targeting downstream molecules of CHEK2 that are involved in the proliferation of cells and the antiapoptosis function of breast tumor cells. Moreover, in addition to prognostic importance, the detection of c.1100delC and I157T mutations can be used as a diagnostic factor in identifying patients with the potential for metastasis of breast tumor cells to other parts of the body.