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Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric
Elise M Fiala1,2, Gowtham Jayakumaran3, Audrey Mauguen4
1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature Cancer
|July 26, 2021
Summary
Germline genetic testing identified pathogenic variants in 18% of pediatric solid tumor patients. These findings support universal germline testing for all children diagnosed with cancer.
Area of Science:
- Oncology
- Genetics
- Pediatric Medicine
Background:
- The role of inherited genetic factors in pediatric cancers is increasingly recognized.
- Understanding germline predisposition is crucial for comprehensive cancer care.
Purpose of the Study:
- To investigate the prevalence and clinical utility of germline pathogenic and likely pathogenic (P/LP) variants in pediatric solid tumor patients.
- To assess the impact of germline testing on clinical management and family testing.
Main Methods:
- Prospective matched tumor-normal DNA sequencing was performed on 751 pediatric solid tumor patients.
- Analysis included variants across low, moderate, and high penetrance genes.
- Clinical actionability and outcomes of positive results were documented.
Main Results:
- Germline P/LP variants were identified in 18% of patients (13% in moderate/high penetrance genes).
- A significant proportion (34%) of high/moderate penetrance variants were unexpected given the patient's diagnosis.
- Positive results led to clinical genetics visits for 76% of patients and cascade testing in 21% of relatives.
Conclusions:
- Germline genetic testing is a valuable tool for identifying cancer predisposition in children with solid tumors.
- Results have implications for patient screening, risk reduction, reproductive decisions, and targeted therapies.
- Universal germline testing should be strongly considered for all pediatric cancer patients.
