Chordoma Family Study

Chordoma is a rare, slow growing, potentially fatal bone tumor derived from remnants of vestigial or ectopic notochord. It occurs almost exclusively in the axial skeleton (skull base, vertebrae, sacrum and coccyx), is somewhat more frequent in males than females, and has a median age at diagnosis of 58.5 years, with a range from early childhood to over 70 years. This typically sporadic tumor usually presents at an advanced stage and the associated mortality is high due to local destruction or distant metastases.

Recently, we identified several families with chordoma in multiple relatives in a pattern consistent with transmission of an autosomal dominant trait. Using clinical and genotyping information from three such families, we mapped a familial chordoma gene to chromosome 7q33. Now, we need to identify more multiplex chordoma families to participate in studies to fine map and clone this gene. To do this, we established collaboration with Dr. Norbert Liebsch, Department of Radiation Oncology (DRO), Massachusetts General Hospital (MGH), Boston. Since 1975, this department has treated ~500 patients with chordoma of the skull base or cervical spine from all over the world; about 400 of these patients speak English.

The proposed study is a pilot study based on up to 80 English-speaking MGH chordoma patients diagnosed age 18 years for whom Dr. Liebsch is the physician of record. We chose this group because of Dr. Liebsch's personal knowledge of the patients and the fact that young age at diagnosis may indicate increased genetic susceptibility to chordoma. A major purpose of the pilot study is to determine the feasibility of conducting a larger study encompassing the remaining (~320) English-speaking MGH chordoma patients. The major goal of the full study would be to identify new multiplex chordoma families to participate in clinical and gene mapping studies.

The data collection components of the pilot study include 1) a family medical history questionnaire completed by each patient/parent or next of kin in person or over the telephone, 2) collecting buccal cells from each patient ~ age 6 years via a mailed buccal cell collection kit, 3) abstracting information about each patient's past medical history from the DRO/MGH medical records, and 4) obtaining paraffin blocks or slides on each chordoma/other primary cancer from the MGH Pathology Department or relevant outside institutions. DNA from buccal cells and tumor will be used for molecular studies.

We will re-contact any family from the pilot study who reports chordoma or astrocytoma in at least one blood relative of the MGH patient. If we confirm these diagnoses we will invite selected family members to participate in clinical and gene mapping studies conducted under a separate NIH approved protocol. We will consider the pilot study to be a success if up to 30- 35 of the 80 chordoma patients/parents/next of kin participate in it, OR if we identify a new multiplex chordoma family that is willing to participate in clinical and gene mapping studies.