CLO20-032: A Founder CHEK2 Pathogenic Variant in Association With Kidney Cancer

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  • a Beacon Medical Group, South Bend, IN
  • b Indiana State University, Terre Haute, IN
  • c Ambry Genetics, SC

The gene CHEK2 codes for the protein checkpoint kinase 2, a known tumor suppressor. When checkpoint kinase 2 is activated as the result of DNA damage, a cascade of protein phosphorylation occurs including Cdc25A, Cdc25C, and BRCA1. The phosphorylation of these substrates leads to either cell cycle arrest, DNA repair, or apoptosis. A pathogenic variant in the gene CHEK2 is known to be associated with an increased lifetime risk of developing male and female breast, colorectal, and prostate cancer. Preliminary literature suggests certain pathogenic variants in the gene CHEK2 may be associated with an increased lifetime risk of developing other cancers, such as papillary thyroid cancer. Four studies in the literature support that a pathogenic variant in the gene CHEK2 may lead to an increased lifetime risk of developing clear cell renal carcinoma. One of these studies, by Cybulski et al, focuses on individuals in Poland with one of three founder variants in CHEK2; IVS2+1G>A, 1100delC, and I157T. Our study supports the association between the presence of a pathogenic variant in the gene CHEK2 and an increased lifetime risk of developing renal carcinoma defined in the Cybulski et al study. Our patient has a personal history of clear cell renal and gastric cancer, a family history of clear cell renal and breast cancer, and was found to have a IVS2+1G>A pathogenic variant in the gene CHEK2. Our patient’s identical twin brother, who also has a history of clear cell renal carcinoma, and two unaffected siblings were also found to have the same pathogenic variant. Our patient has another sibling who also had a history of clear cell renal carcinoma, but was deceased before genetic testing was completed. This case study supports the limited evidence that a pathogenic variant in the gene CHEK2 may be associated with an increased lifetime risk of developing clear cell renal carcinoma. If this association is established through further research, it could impact the testing and cancer screening that a healthcare provider would recommend when they obtain a family history that has numerous members with clear cell renal cancer. It could also impact medical management recommendations for patients who are found to have a pathogenic variant in CHEK2; therefore, leading to a more comprehensive medical management plan for the patient.

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Corresponding Author: Kassi Brooks, MS
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