Assessment of cancer predisposition syndromes in children with leukemia and solid tumors: germline-genomic profiling and clinical features in a series of cases

Cancer predisposition syndromes (CPS) are a group of genetic disorders that increase the risk of various cancers. Identifying CPS has a significant impact on the treatment plan, screening and follow-up strategy, and genetic counseling of the family. However, in children, it goes underdiagnosed in most clinical setups, especially in low- and middle-income (LMIC) countries. In the present study, we screened 60 pediatric oncology patients for a possible CPS based on pre-defined selection criteria. Six patients met the criteria, three of whom had hematological malignancy, while the remaining three had sarcoma. Whole exome sequencing was performed in the selected patients to confirm the diagnosis. Germline mutation in CPS-related genes was discovered in five of six cases, including novel mutations discovered in two. An adverse outcome was observed in all five patients with underlying cancer predisposition syndrome, with three having relapsed and two having progressive disease. Our study reflects a prevalence of 10% underlying CPS in a limited cohort of patient based on the phenotype-genotype approach in our cohort. Using pre-defined clinical selection criteria, screening can be directed to a high-risk patient cohort with high-pick up rate for CPS. The selection criteria could be utilized in any LMIC-based clinical setup for pediatric cancer patients who may benefit from modification of treatment as well as genetic counseling.