Trial Information

The Chordoma Family Study: A Pilot Collaboration Between NCI and Massachusetts General Hospital (MGH) to Identify Chordoma Families

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.