Know Cancer

or
forgot password

BRCA1 Haploinsufficiency and Gene Expression


N/A
N/A
N/A
Not Enrolling
Female
BRCA1 Mutations

Thank you

Trial Information

BRCA1 Haploinsufficiency and Gene Expression


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.


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.

Type of Study:

Observational

Study Design:

Observational Model: Case Control, Time Perspective: Prospective

Outcome Measure:

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.

Outcome Time Frame:

5 years

Safety Issue:

No

Principal Investigator

Tari King, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

04-045

NCT ID:

NCT00597987

Start Date:

September 2004

Completion Date:

September 2012

Related Keywords:

  • BRCA1 Mutations
  • BRCA1

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021