Assessing Recurrent Genomic Aberrations Linked to Ethnicity
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The National Cancer Institute reports the lifetime risk of breast cancer for women in the US is 13.3%. While the incidence of breast cancer in African Americans is about 20% lower than that in Caucasians, the prognosis in African-Americans with breast cancer is 20% poorer than in Caucasians. Population-based studies have shown that African-American women tend to have tumors that are larger, more advanced in stage and have higher lymph node involvement and more distant metastasis compared to Caucasian women. Some of these differences can be related to socio-economic and reproductive differences. However, these factors do not explain why breast cancers in African American are more poor-differentiated and estrogen receptor-negative, regardless of menopausal status. We postulate that these characteristics are due to fundamental differences in cancer genotype that arise during tumor development. If true, different approaches to treatment may be warranted.
 
 
 
 
 
 
 
 We have analyzed genome copy number aberrations in about 150 breast cancers using microarray-based Comparative Genomic Hybridization (array CGH). These analyses suggest that some genomic differences do exist between African American and Caucasian tumors, although only 11 tumors from African-Americans were included in the study compared to tumors from 108 Caucasians. The purpose of this study is to validate these findings in a larger set of tumors and to test the hypothesis that ethnicity related aberrations cause gene expression changes that contribute to biological events that are associated with reduced survival in African American women with breast cancer. These studies also will identify gene expression differences between tumors from Caucasian and African American women that are caused by epigenetic and other non-genomic events.
 
 
 
 
 
 
 
 I will use array CGH to identify map gene dosage aberrations and Affymetrix gene expression arrays to compare breast tumors from African American and Caucasian women. I will focus on poorly differentiated tumors with estrogen receptor-negative that is dominant type in African American tumors. I will obtain 50 matched tumor samples each of African American and Caucasian from the UCSF Cancer Center and the University of Alabama to identify the racial difference in recurrent genomic aberrations and gene expression. DNA for the CGH study and RNA for the expression assay will be extracted from same tumor samples. The gene expression will be measured using Affymetrix GeneChip? microarrays to assess the expression of ~40,000 genes in each sample. CGH arrays will interrogate copy number over the genome with ~1 MB resolution along the genomic distance.
 
 
 
 
 
 
 
 This project will apply state-of-the-art technologies to identify genomic and gene expression differences between breast cancers that arise in African Americans and Caucasians. These will be the first comparative genomic and gene expression analyses on these tumor types. These studies will identify the extent to which prognostic markers and therapeutic strategies developed through analyses of tumors from Caucasian women will apply to tumors that arise in African American women.