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

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00341627
First received: June 19, 2006
Last updated: September 6, 2014
Last verified: August 2014
  Purpose

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.

Recently, we have identified and studied one large family in which 10 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 have tentatively napped this gene to the long arm of chromosome 7. To confirm this finding, and to fine map and clone the gene, we need 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 include 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 will carry out all the data collection activities for the study subjects identified through the Detroit registry. NCI will also conduct 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 will send 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.


Condition
Chordoma

Study Type: Observational
Official Title: Genetic Aspects of Chordoma: A Collaboration With SEER Registries to Identify Chordoma Families

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 140
Study Start Date: January 1999
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

All persons with chordoma reported to the four tumor registries from January 1988 to the end of the study period.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00341627

Locations
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
Investigators
Principal Investigator: Mary L McMaster, M.D. National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00341627     History of Changes
Other Study ID Numbers: 999999005, OH99-C-N005
Study First Received: June 19, 2006
Last Updated: September 6, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Bone Tumor
Familial
Gene Mapping
Genetics
Sporadic

Additional relevant MeSH terms:
Chordoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on October 19, 2014