Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Background: To identify molecular factors associated with survival disparities, multiple studies have identified differentially expressed genes in tumors from African American women (AAW) compared to Caucasian women (CW), however, it is not clear whether these changes, such as increased expression of PHSPL, SOS1 and CRYBB2P1 in tumors from AAW, are clinically meaningful or represent population artifact. Gene expression data were thus evaluated in breast tumors with defined intrinsic subtypes, non-malignant breast tissue and blood from patients without breast disease.</jats:p>
<jats:p>Methods: Gene expression data was generated using U133 2.0 microarrays for 184 breast tumors from AAW and CW matched by subtype, grade, age and presence of local or distant metastases, from 44 benign biopsy specimens, and from 143 peripheral blood samples from patients without current or past invasive breast disease. Principal component analysis (PCA) was performed using Partek Genomics Suite 6.6 and differentially expressed genes were detected using ANOVA with FDR&lt;0.05, 2-fold difference defining significance.</jats:p>
<jats:p>Results: When all tumors were analyzed together, only PSPHL, CRYBB2P1 and SOS1 were differentially expressed, each at significantly higher levels in tumors from AAW. When analyzed by subtype, PSPHL, CRYBB2P1, SOS1 and AMFR were expressed at higher levels in luminal A tumors (n=86) and SOS1 at higher levels in basal-like tumors (n=66) from AAW; no differentially expressed genes were detected in HER2-enriched (n=18) or luminal B (n=14) tumors. AMFR, CRYBB2P1, PSPHL and SOS1 were also expressed at significantly higher levels in both non-malignant breast tissue from AAW patients, and in blood specimens from disease-free AAW patients compared to non-malignant and blood specimens from CW.</jats:p>
<jats:p>Conclusions: PCA demonstrates that molecular profiles of tumors from AAW are highly similar to those from CW; the few genes that are differentially expressed in tumor specimens are not associated with breast cancer as the same changes are also found in disease-free breast tissues as well as blood from patients without breast disease. Lack of meaningful genetic differences, even within specific tumor subtypes, suggests that disparity differences between AAW and CW with breast cancer are not attributable to molecular differences inherent to the tumors, but likely stem from other factors such as genetic predisposition to the development of basal-like tumors or altered provision of or response to treatment.</jats:p>
<jats:p>Citation Format: Allyson L. Valente, Craig D. Shriver, Rachel E. Ellsworth. Gene expression profiling of breast tumors from African American and Caucasian women: Are molecular differences meaningful. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3270. doi:10.1158/1538-7445.AM2014-3270</jats:p>