CHEK2 and Pediatric Cancer Predisposition
Clinical Genetics and Therapeutics
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Primary Categories:
- Cancer
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Secondary Categories:
- Cancer
Introduction:
Cell cycle checkpoint kinase 2 (CHK2) plays a role in cell cycle arrest, which is activated in response to DNA damage. Mutations in the CHEK2 gene are autosomal dominantly inherited, and historically have been associated with adult-onset cancer predisposition, particularly low to moderate risk breast cancer (20%-40%). As such, pediatric oncology patients and their siblings are not frequently tested for mutations in this gene, and therefore, less is known about the role it plays in pediatric cancer predisposition.
Methods:
We identified several children in our patient cohort who were diagnosed with a variety of cancers for whom a CHEK2 germline mutation was identified. Additionally, we reviewed the medical literature for other children diagnosed with cancer who were found to harbor a germline CHEK2 mutation and amalgamate our findings herein. Search terms in the medical literature included CHEK2, germline, pediatric, and individual tumor types.
Results:
A total of 140 pediatric oncology patients were identified as having a germline CHEK2 mutation including six individuals from our patient population and 134 subjects reported in the medical literature. Cancers spanned the entire tumor spectrum: 46% solid tumors, 25% blood cancers, 25% brain/CNS tumors, and 4% lymphoma, of which there were ~35 different types of cancer. Among these, B-cell ALL was most common (18%), followed by neuroblastoma (12%), Wilms tumor (8%), thyroid cancer (6%), and non-specific brain tumors (6%). Surprisingly, CHEK2 mutations were found among children with high and lower grade brain tumors, e.g., medulloblastoma (n=5), high grade glioma (n=5), and pilocytic astrocytoma (n=4), as well as tumors not commonly associated with a predisposition syndrome including Ewing sarcoma (n=7).
Conclusion:
Testing for germline mutations in CHEK2 should not be reserved for adults and should be considered as part of the gene differential for pediatric oncology patients undergoing germline testing. More research is needed to explore the role that germline CHEK2 mutations play in pediatric cancer predisposition. So too, further studies are needed to develop surveillance practices for the pediatric population.
Cell cycle checkpoint kinase 2 (CHK2) plays a role in cell cycle arrest, which is activated in response to DNA damage. Mutations in the CHEK2 gene are autosomal dominantly inherited, and historically have been associated with adult-onset cancer predisposition, particularly low to moderate risk breast cancer (20%-40%). As such, pediatric oncology patients and their siblings are not frequently tested for mutations in this gene, and therefore, less is known about the role it plays in pediatric cancer predisposition.
Methods:
We identified several children in our patient cohort who were diagnosed with a variety of cancers for whom a CHEK2 germline mutation was identified. Additionally, we reviewed the medical literature for other children diagnosed with cancer who were found to harbor a germline CHEK2 mutation and amalgamate our findings herein. Search terms in the medical literature included CHEK2, germline, pediatric, and individual tumor types.
Results:
A total of 140 pediatric oncology patients were identified as having a germline CHEK2 mutation including six individuals from our patient population and 134 subjects reported in the medical literature. Cancers spanned the entire tumor spectrum: 46% solid tumors, 25% blood cancers, 25% brain/CNS tumors, and 4% lymphoma, of which there were ~35 different types of cancer. Among these, B-cell ALL was most common (18%), followed by neuroblastoma (12%), Wilms tumor (8%), thyroid cancer (6%), and non-specific brain tumors (6%). Surprisingly, CHEK2 mutations were found among children with high and lower grade brain tumors, e.g., medulloblastoma (n=5), high grade glioma (n=5), and pilocytic astrocytoma (n=4), as well as tumors not commonly associated with a predisposition syndrome including Ewing sarcoma (n=7).
Conclusion:
Testing for germline mutations in CHEK2 should not be reserved for adults and should be considered as part of the gene differential for pediatric oncology patients undergoing germline testing. More research is needed to explore the role that germline CHEK2 mutations play in pediatric cancer predisposition. So too, further studies are needed to develop surveillance practices for the pediatric population.