BRCA1 Haploinsufficiency and Gene Expression

This study has been completed.
Sponsor:
Collaborator:
Memorial Health University Medical Center
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00597987
First received: January 9, 2008
Last updated: September 12, 2012
Last verified: September 2012
  Purpose

The purpose of this study is to collect a blood sample from patients that may be used for research purposes. These blood samples will be used by researchers at this institution to study the causes of breast and ovarian cancer, and to better understand how these cancers develop. We are trying to discover differences in the ways cells work in women with a high genetic risk of developing breast or ovarian cancer. Early data suggest that some genes may be turned on or off in different ways based upon whether or not a woman has a high genetic risk of developing breast or ovarian cancer. The primary objective is to test the hypothesis that BRCA1 haploinsufficiency regulates gene expression on the X chromosome. This hypothesis will be tested by comparing the gene expression profiles of BRCA1 heterozygotes (cases) to an age-matched group of unaffected women who are not BRCA1 mutation carriers (controls).


Condition
BRCA1 Mutations

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: BRCA1 Haploinsufficiency and Gene Expression

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • The primary analysis of these data will be paired t-tests between the age-matched cases and controls for all genes on the X chromosome. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood samples from cases will be collected from patients who have previously undergone genetic counseling through the Clinical Genetics Service at MSKCC and tested positive for a germline mutation in BRCA1. Blood samples from controls will be obtained from two sources.

First from specimens already collected under IRB Protocol #99-030, entitled "Collection of Tissue, Blood, and Cells to be Used for Studying the Causes, Prevention, Diagnosis, and Treatment of Breast Cancer (T. King, PI). Controls will also be collected from patients who have previously undergone genetic counseling through the Clinical Genetics Service at MSKCC and tested negative for germline mutations in BRCA1. Isolation of total RNA from blood will be performed using the PAXgene™ Blood RNA System. This study will use lymphocyte RNA samples from 50 individuals with BRCA1 mutations and 50 age-matched controls. Gene expression profiling will be performed in the Genomics Core Laboratory of MSKCC.


Enrollment: 120
Study Start Date: September 2004
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
RNA samples

Detailed Description:

The specific aim of this project is to test the hypothesis that BRCA1 haploinsufficiency regulates gene expression on the X chromosome. This hypothesis will be examined by determining if X chromosome gene expression profiles, derived from lymphocyte RNA, of BRCA1 mutation carriers (cases) can be distinguished from an age-matched group of women who do not have BRCA1 mutations (controls). Neither cases nor controls will have a history of cancer. This investigation will provide valuable insight into the biologic function of BRCA1 and its role in breast and/or ovarian tumorigenesis. Blood samples from cases will be collected from patients who have previously undergone genetic counseling through the Clinical Genetics Service at MSKCC and tested positive for a germline mutation in BRCA1. Blood samples from controls will be obtained from two sources.

First from specimens already collected under IRB Protocol #99-030, entitled "Collection of Tissue, Blood, and Cells to be Used for Studying the Causes, Prevention, Diagnosis, and Treatment of Breast Cancer (T. King, PI). Controls will also be collected from patients who have previously undergone genetic counseling through the Clinical Genetics Service at MSKCC and tested negative for germline mutations in BRCA1. Isolation of total RNA from blood will be performed using the PAXgene™ Blood RNA System. This study will use lymphocyte RNA samples from 50 individuals with BRCA1 mutations and 50 age-matched controls. Gene expression profiling will be performed in the Genomics Core Laboratory of MSKCC under the supervision of Agnes Viale, PhD. Class comparison analysis will be performed on the gene expression data in the Biostatistics Department under the supervision of Adam Olshen, PhD. It is anticipated that this study will be completed in approximately 1 year.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

The study will be performed using lymphocyte RNA samples from 50 women with BRCA1 mutations and 50 age-matched controls without BRCA1 mutations. Class comparison analysis will be performed on the gene expression data.

Criteria

Inclusion Criteria:

For acquisition of control specimens, samples already collected under IRB approved protocol 99-030 will be used. This protocol was a tissue and blood acquisition protocol entitled "Collection of Tissue, Blood, and Cells to Be Used for Studying the Causes, Prevention, Diagnosis, and Treatment of Breast Cancer". Patients have already given consent and signed a research authorization for to use their blood specimens for this purpose. Controls will also be collected from patients who have previously undergone genetic counseling through the Clinical Genetics Service at MSKCC and tested negative for a germline mutations in BRCA1. These individuals will be approached and asked to donate a sample at the time of their results appointment. Blood samples from cases will be collected from patients who have tested positive for a germline mutation in BRCA1. These women will have been participants in MSKCC protocols such as 96-51 and 97-29, or tested at outside institutions and receiving followup care at MSKCC. Any patient with a presumed pathogenic mutation in BRCA1 will be eligible for inclusion.

Exclusion Criteria:

Subjects will be eligible without regard to age, racial, or ethnic status. Subjects with any personal history of cancer will be excluded. Attending physicians authorized to obtain informed consent may exercise discretion in excluding individuals for appropriate medical or other (e.g., minors, mentally impaired) reasons. Patients with an unclassified variant in BRCA1 will be excluded as the functional significance of these variations is unknown.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00597987

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Memorial Health University Medical Center
Investigators
Principal Investigator: Tari King, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00597987     History of Changes
Other Study ID Numbers: 04-045
Study First Received: January 9, 2008
Last Updated: September 12, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
BRCA1

ClinicalTrials.gov processed this record on August 21, 2014