THE MOLECULAR BASIS OF ROTHMUND-THOMSON SYNDROME AND OSTEOSARCOMA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Certain genetic syndromes are known to predispose affected patients to cancer more than the general population. Rothmund-Thomson syndrome (RTS) is one of these cancer syndromes and specifically predisposes patients to developing osteosarcoma (OS), a primary bone tumor that occurs in children and adolescents. Mutations in a gene called RECQL4 accounts for two-thirds of cases of RTS; however, for the other one-third of patients, the gene defect has not yet been discovered. We are interested in studying patients with RTS and related syndromes, as well as patients with atypical forms of OS, in order to understand the molecular mechanisms underlying OS predisposition and pathogenesis. This study would allow the collection of samples and medical information from patients with RTS and related disorders and their family members, as well as from patients with atypical osteosarcoma that may have a genetic basis, so that molecular and genetic studies can be conducted to better understand the primary syndrome (RTS), the predisposition toward cancer development, as well as the molecular pathogenesis of OS. Studying rare cancer predisposition syndromes (RTS) both at the clinical and molecular level will provide insight into the pathogenesis of cancer (OS) in the general population. Specific Aim 1: Collect and analyze clinical samples from patients affected by RTS and related syndromes and atypical forms of OS as well as their family members. Samples would include blood, tissues (normal and tumor) and body fluids which would be made available to investigators for the purpose of conducting research that will help to define and characterize the underlying genetic defects which cause these inherited disorders and their propensity toward cancer. Specific Aim 2: Collect and analyze medical records from patients affected by RTS and related syndromes and atypical forms of OS as well as their family members. Clinical information will allow genotype-phenotype analyses in combination with molecular studies.