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.
Observational Model: Case Control, Time Perspective: Prospective
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.
Tari King, MD
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
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