Genome-wide sequencing for the identification of potential genomic denominators between tumorgenesis factors in neuroblastoma and differentiated thyroid carcinoma in children

Recently, three neuroblastoma (NBL) survivors have been diagnosed with
papillary thyroid carcinoma in our center. All of them had received treatment
with 131I-MIBG. It has been extensively described that exposure to 131I ¯ may
result in thyroid damage, such as hypothyroidism, nodules and differentiated
thyroid carcinoma (DTC). To prevent uptake of radio-iodide into the thyroid
gland during 131I-MIBG treatment, NBl patients are given thyroid protection Of
the 3 patients here described, 2 patients had received potassium-iodide (KI)
during MIBG administration and 1 patient was given a combination drug
protection consisting of KI, Methimazole and L-thyroxine (dilute, block and
replace (DBR).
On the MIBG scans of these 3 children, no uptake of radio-iodide was seen in
the thyroid gland during exposure to MIBG. For this reason, other causes than
radiation damage for DTC to occur in these children must be considered, such as
genetic predisposition. Another argument that may support this hypothesis is
the fact that after external radiation, DTC is more often diagnosed in NBL
survivors than in other childhood cancer survivors. We hypothesize that
children with NBL are inherently at an increased (genetic) risk to develop DTC,
irrespective of previous radiation exposure.

To detect potential genomic denominators between tumorgenesis factors in
neuroblastoma and differentiated thyroid carcinoma.

Observational study into the existence of genomic denominators between
tumorgenesis factors in neuroblastoma and differentiated thyroid carcinoma
(through whole genome sequencing).

Burden/risk/benefits:
The risk for the probands in this study (children and parents) is considered
minimal. During a vena puncture blood with be withdrawn for whole-genome
sequencing. Patients and their parents will get genetic counseling prior to
whole genome sequencing. Important issues to discuss include:
- Basic genetics (cells, genes, chromosomes, mutations etc.)
- (Incidental) findings

Group relatedness:
Because of the fact that neuroblastoma only occur during childhood, research to
the identification of potential genomic denominators between tumorgenesis
factors in neuroblastoma and differentiated thyroid carcinoma has to be
performed in children, thereby involving minors.