To identify novel childhood osteosarcoma predisposing genes.
ID
Source
Brief title
Condition
- Skeletal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Understanding the molecular etiology and pathogenesis of CRC in AYAs is
expected to yield novel genetic risk factors. that will facilitate clinical
decision making, including early tumor detection, in AYAs with CRC and their
siblings at risk.
Secondary outcome
Identification of novel genetic risk factors voor CRC will facilitate clinical
decision making, including early tumor detection in AYAs with CRC and their
siblings at risk.
Background summary
Osteosarcoma is the sixth leading cause of death in children under the age of
15 years. Several genetic syndromes are known to predispose children to
osteosarcoma, e.g. Rothmund Thompson syndrome, Li Fraumeni syndrome, and
Retinoblastoma predisposition syndrome. These syndromes are often easily
recognizable by a positive family history for cancer or additional features in
the patient. The role of cancer predisposition in children with sporadic
osteosarcoma, hence without additional features or positive family history, is
unknown.
Study objective
To identify novel childhood osteosarcoma predisposing genes.
Study design
We will apply whole exome sequencing on germline DNA of the child with
osteosarcoma and both parents. This *trio analysis* enables us to specifically
search for de novo and autosomal recessive changes in the DNA of the child,
which are likely scenarios for genetic predisposition in sporadic cases. In
addition we will perform whole genome sequencing on tumor DNA. The tumor data
will support the identification of osteosarcoma predisposing germline variants,
for example by finding genes with second hit mutations in the tumor and by
defining recurrent subclasses of osteosarcomas that share somatic mutations or
molecular pathways that could be associated with specific deleterious variation
in the germline. Candidate genes will be screened in a validation cohort of
germline samples from osteosarcoma patients as well as other childhood cancer
patients that are available for this study through collection by the AGORA
biobank.
Study burden and risks
The risk of this study is considered to be negligible. The only physical burden
is a venepuncture. There is a small risk of unsolicited findings when exome or
genome sequencing is performed. Patients and/or their caretakers will be
thoroughly counselled about these risks and possible psychosocial consequences.
Furthermore the protocol that is used for unsolicited findings has already been
established in the department of Clinical Genetics and is approved by the
Commissie Mensgebonden Onderzoek Regio Arnhem-Nijmegen (ref CD/CMO 0507).
Geert Grooteplein 10
Nijmegen 6500HB
NL
Geert Grooteplein 10
Nijmegen 6500HB
NL
Listed location countries
Age
Inclusion criteria
20 individulas who have developed osteosarcoma in childhood (<19 years of age) without a syndrome diagnosis after consultation by a clinical geneticist, and their parents.
Exclusion criteria
- A proven osteosarcoma predisposing condition
- A genetic defect in the family for a cancer unrelated condition, of which the child might be a carrier but about which the child/parents do not want to be informed.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL53280.091.15 |