Clinical and molecular characterization of childhood cancer susceptibility syndromes

At present, the etiology of most childhood malignancies is unknown. Based on an
overall increase in the Standard Incidence Ratio (SIR; 1.1-1.8) of first-degree
relatives in the population of children with malignancies, a certain degree of
genetic predisposition is anticipated.
Recently it was established that 8% of the children with a malignancy suffer
from an additional congenital malformation syndrome. These percentages are
significantly higher than the 1 % observed in the general population, and
strongly underline the notion that constitutional anomalies may be associated
with the occurrence of pediatric malignancies.

To identify novel childhood cancer-predisposing genes in children.

Since patients with a malignancy and a congenital malformation syndrome are
likely to exhibit genomic anomalies (microdeletions and/or duplications) that
are within the limits of detection by microarray-based comparative genomic
hybridization (arrayCGH) array, such patients are particularly well-suited for
the discovery of novel cancer-predisposing genes. We will apply whole genome
arrayCGH technology to the identification of novel candidate genes in children
with a malignancy and one or more phenotypic abnormalities and/or a positive
family history for cancer.

The risks associated with participating in this study are minimal. The
interview of patients/parents includes questions covering medical history and
family history concerning malignancies; It poses no risk (physical or
psychological) to the individual. Blood is drawn by a clinician. There is a
minimal risk associated with venapuncture: slight pain and possible bruising,
infection.
A firm genetic diagnosis will allow genetic counseling within families and may
answer questions concerning the risk to develop malignancies in other children
within such families.