Trial Information

Genetic Aspects of Chordoma: A Collaboration With SEER Registries to Identify Chordoma Families

Chordoma is an uncommon (400 case/year in the U.S.) and potentially fatal bone tumor derived
from remnants of embryonic notochord. It occurs primarily in the axial skeleton and has a
mean age at diagnosis of 55 years, with a range from early childhood to over 70 years. This
tumor usually presents at an advanced stage and the associated mortality is high due to
local destruction and distant metastases. Chordoma is rare in African-Americans and is
typically sporadic; there are few reports of these tumors arising congenitally or within
members of the same family.

In 1996, we have identified and studied one large family in which 8 relatives in three
generations have chordoma; the inheritance pattern suggests transmission of a mutation in an
autosomal dominant gene. Using information from this family, we tentatively mapped this
gene to the long arm of chromosome 7. To confirm this finding, and to fine map and clone
the gene, we needed to study additional chordoma families.

In an effort to identify such families, we have developed collaborations with four SEER
registries covering the populations of Detroit, Los Angeles, Iowa, and New Mexico. Each
registry will identify all chordoma cases diagnosed since 1988 and invite them (or the next
of kin of deceased cases) to participate in our study. Through 1997, the registries have
identified a total of 140 chordoma cases, 96 of whom are living. The registries will invite
these patients (or their next of kin) to participate in the study. The study components
included completion of a self-administered personal and family medical history
questionnaire, retrieval of medical records and pathology reports pertaining to chordoma,
and collection of paraffin-embedded chordoma tissue and buccal mucosal cells for genetic
studies. NCI carried out all the data collection activities for the study subjects
identified through the Detroit registry. NCI also conducted the buccal cell collection
component of the study for all patients identified by the other three registries. These
three registries will carry out all other study activities on these patients/next of kin and
sent the data and slides prepared from the paraffin blocks to NCI. NCI will analyze the
questionnaire data to determine if any unusual patterns of cancers other than chordoma or
other medical conditions appear to cluster in families of the chordoma patients. Selected
members of any families with two or more relatives with chordoma will be invited to
participate in a separate clinical and molecular study conducted at NIH to try to identify
the chordoma gene. DNA from the buccal cells and tumor blocks from all other patients with
'sporadic' chordoma identified through the registries (likely to comprise most patients)
will not be studied until we or others have identified such a gene.