Child Cancer Predisposition

The cause of cancer development remains largely unknown and can be attributed to lifestyle and intrinsic, environmental and genetic factors. It is estimated that 10% of childhood cancer patients carry a known hereditary alteration causing a cancer predisposition syndrome. Identification of such predisposing factors can improve treatment decisions, prevention and surveillance, follow-up and psychosocial support. In general, a childhood cancer predisposition syndrome can be suspected in the following situations: (1) a familial or personal history of cancer, (2) a type of cancer that is typically associated with predisposition syndromes and (3) the presence of congenital or other anomalies (for example overgrowth syndrome, immune deficiencies).

Although a number of hereditary alterations and their associated predisposition syndromes or malignancies have already been identified, it is likely that more patients are yet to be recognized. First, children and adolescents with cancer have a limited exposure to environmental or lifestyle factors and second, the absence of identifiable alterations in patients with an obvious familial history or other clinical signs is an indication for the presence of undiscovered heritability.

The development of next-generation sequencing technologies, such as whole exome and whole genome sequencing, has revolutionized the ability to unravel molecular mechanisms underlying cancer development. DNA sequencing approaches allow us to read the human genetic code and bring the possibility to discover novel cancer predisposing alterations.

In this research, DNA sequencing is used to unravel novel genetic alterations associated with cancer predisposition in patients and families at risk for genetic susceptibility. In a next step, their role in cancer development is investigated in more detail using different cancer modeling techniques and functional lab experiments. Ultimately, this will provide important insights into both cancer and normal developmental biology and offers opportunities for targeted therapies

Latest publication

Derpoorter C, Van Paemel R, Vandemeulebroecke KVanhooren J, De Wilde B, Laureys G and Lammens T. (2022). Whole genome sequencing and inheritance-based variant filtering as a tool for unraveling missing heritability in pediatric cancer. Pediatric Hematol. Oncol. 40 (4): 326-340. DOI: 10.1080/08880018.2022.2101723. PMID: 35876323