Germline pathogenic/likely pathogenic mutations and subsequent neoplasms among childhood cancer survivors

The ALTE03N1 study by the Children’s Oncology Group found that among childhood cancer survivors (CCSs) the risk of developing subsequent neoplasms (SNs) was 4.26-fold higher in carriers of pathogenic/likely pathogenic (P/LP) mutations. Addition of P/LP mutation status to the clinical risk classifier was associated with significant performance improvement. Overall, 86.4% of the CCSs with any P/LP mutation, and all TP53 and RB1 mutation carriers were partitioned into the moderate-to-high SN risk group. The authors conclude that these findings provide a risk-based approach for identifying CCSs who could be referred for genetic testing, informing surveillance strategies on the basis of refined risk classification.