Checkpoint Kinase 2 (CHEK2) Mutation in Renal Cell Carcinoma: A Single-Center Experience

Abstract

Renal cell carcinoma (RCC) occurs in sporadic and heritable forms. Genetic mutations have been identified as risk factors in 1–2% of RCC. The aim of this study was to evaluate I157T and CHEK2*1100delC mutations of checkpoint kinase 2 (CHEK2) gene in RCC. Medical records of 40 clear cell RCC patients who had genetic tests and consultation at the Genetic Outpatient Clinic, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland, were reviewed retrospectively. Mutation profile was assessed by ASA-PCR and RFLP-PCR techniques. Only three female patients had CHEK2 mutation (I157T). No CHEK2*1100delC was observed in any of the patients. These tumors were N0, and two were Grade 3. One showed capsular infiltration. No blood vessel infiltration or metastases was observed. Overall, RCC from patients with CHEK2 mutation did not display any special characteristics when compared with those without the mutation. While no association between CHEK2 mutation and RCC could be established, all three patients with CHEK2 mutation developed second neoplasms many years after first diagnosis. Further studies, especially regarding CHEK2 mutation as a predictive factor for second neoplasm in RCC patients, are warranted.

Prevalence of pathogenic variants in DNA damage response and repair genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer

“…The most common gene with PVs identified in the patients in this study was the DDRR gene, CHEK2 (19/844, 2.25%). This is consistent with recent reports by Carlo et al and Huszno et al 15 , 16 . While evidence is mounting that CHEK2 PVs may increase risk for RC, in this study we did not consider CHEK2 as a gene typically associated with RC as it is not currently included on RC panels and would fail to be included in testing in many cases.…”

Is CHEK2 a moderate-risk breast cancer gene or the younger sister of Li-Fraumeni?

“… 18 However, literature around CHEK2 1100delC is less clear. According to Näslund-Koch et al , 10 CHEK2 *1100delC HR for kidney cancer is 3.45 (95% CI 1.09–10.9) that supports the theory of driving renal cell cancer, but CHEK2 *1100delC was not observed in any of the patients with renal cell cancer in Huzano and Kolosza, 19 therefore, the data supporting the role of CHEK2 *1100delC are conflicting. 10 17 19 …”

“…18 However, literature around CHEK2 1100delC is less clear. According to Näslund-Koch et al, 10 CHEK2*1100delC HR for kidney cancer is 3.45 (95% CI 1.09-10.9) that supports the theory of driving renal cell cancer, but CHEK2*1100delC was not observed in any of the patients with renal cell cancer in Huzano and Kolosza, 19 therefore, the data supporting the role of CHEK2*1100delC are conflicting. 10 17 19 The link between CHEK2 mutation and gliomas is plausible because of its role as a tumour suppressor gene; case reports published suggest CHEK2 mutation as the possible cause of medulloblastomas, 20 as well as primary gliomas and astrocytomas.…”

Prevalence of pathogenic variants in DNA damage response genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer

“…This population is particularly likely to be interested in evaluation of genetic risk. Further, germline PVs in some DDR genes have been observed in RC, including the DNA mismatch repair (Lynch syndrome) genes MSH2 and MLH1 in renal urothelial carcinoma, and CHEK2 in advanced renal cell carcinoma (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). To address the hypothesis that PVs in DDR genes may contribute to the missing heritability of eoRC, we analyzed germline sequencing data from a cohort of 844 eoRC, many of whom had additional non-RC primary tumors or a family history of non-RC cancers.…”