Centrosome amplification has long been established as a hallmark of cancer. More than 80% of invasive breast tumors display this cellular trait. Centrosomal aberrations underlie chromosome instability (CIN) thus corroborating the extensive clonal intratumoral heterogeneity existent within breast lesions that fuels tumor evolution. Sub-clonal heterogeneity drives emergence of aggressive clones with a propensity to migrate and invade, resulting in tumor dissemination and metastases. Thus, centrosome amplification is a critical driver of tumor progression and metastases. Although numerous studies have linked centrosomal overload to tumor aggressiveness, no studies have yet quantified this cell-biological feature to establish a well-defined relationship between the severity and extent of centrosome amplification and tumor aggressiveness. Utilizing an innovative and rationally-guided approach, we have derived an algorithm that allows the precise quantitation of the frequency and severity of both structural and numerical aberrations in supernumerary centrosomes present in clinical samples. Our novel method thus uncovers previously unrecognized differences in the centrosomal profiles of grade-matched breast tumors from African-American (AA) (n=71) and European American (EA) (n=104) women. Our data demonstrate that AA breast tumors exhibit higher numeral, structural and total centrosome amplification scores than grade-matched EA tumors. Interestingly, tumors displaying lymph node and distant metastasis exhibited higher structural amplification than grade-matched non-metastatic tumors. Hence, our novel quantification tool offers valuable information that can potentially predict the risk of AA breast tumors rapidly progressing to metastatic disease and uncovers a hitherto unappreciated organelle-specific disparity marker among racially distinct breast tumors.

This abstract was also presented as Poster B6.

Citation Format: Nikita Wright, Vaishali Pannu, Padmashree Rida, Karuna Mittal, Sergey Klimov, Farida N. Yada, Michelle D. Reid, Guilherme Cantuaria, Ritu Aneja. Disparities in centrosomal profiles: Prediction of metastatic risk in African American and European American breast cancer patients. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr PR13.

©2015 American Association for Cancer Research.
2015