Abstract B081: Common copy number aberrations in breast cancer in Latinas
Authors: Ziv Elad , Schmolze Daniel , Hu Donglei , Adamson Aaron , Tao Shu , Adams Charleen , Steele Linda , Huntsman Scott , Weitzel Jeffrey , Byun Jung , Gardner Kevin , Perez-Stable Eliseo , Napoles-Springer Anna , Neuhausen Susan 
Published: September 2020

Abstract
Background: Latinos represent the largest and fastest-growing minority population in the US; breast cancer is the most common cancer and causes the most cancer deaths in this population. Copy number amplifications and deletions are an important determinant of the biology of breast tumors and, in some cases, may help to guide treatment. However, little is known about the copy number profile of breast tumors from Latinas. For example, in The Cancer Genome Atlas (TCGA), one of the largest publicly available tumor mutation datasets, there are data on only 31 Latina (out of a total of &gt;1000) breast cancer cases. Therefore, we used whole exome sequencing on matched tumor/normal pairs in 146 tumors from 142 women, to investigate copy number aberrations in breast tumors from Latinas. Methods: We enrolled 142 Latinas with invasive breast cancer and obtained blood and tumor tissue (formalin-fixed paraffin embedded). We performed whole exome sequencing of 146 pairs of tumor (somatic) and normal (germline) samples resulting in 142 tumor-normal pairs for analysis. Target coverage for normal was ~30X and for tumor was ~100X. Sequence data were aligned using Burrows-Wheeler Aligner, and copy number aberrations were called using CNVkit. We estimated genetic ancestry from the germline genotype data using ADMIXTURE. Results: Age at diagnosis ranged from 31 to 75 years with a median age of 48 years. Histologically, 83% were estrogen-receptor positive, 71 % were progesterone-receptor positive, and 17% were human epidermal growth factor receptor positive; 87% were Stage 1 or 2 at diagnosis. The mean genetic ancestry in our sample was ~52.3% European, ~41.6% Indigenous American, and ~6.2% African. Large copy number amplifications were detected mostly commonly at 1q and 8q, and large deletions were detected at 11q, 16q and 17p. Genes commonly gained/amplified included MYC (43%), FGFR1 (19.2%), CCND1 (18.0%), and ERRB2 (14.4%). Genes commonly deleted in at least one chromosome include TP53, MAP2K4, BRCA1, PP2R2A, CHEK2, and PALB2. Summary: Breast tumors from Latinas display similar rates of large chromosomal copy number gains and losses at common positions and similar rates of gene-specific copy number amplifications and deletions compared non-Latina European ancestry women.
Citation Format: Elad Ziv, Daniel Schmolze, Donglei Hu, Aaron Adamson, Shu Tao, Charleen Adams, Linda Steele, Scott Huntsman, Jeffrey Weitzel, Jung Byun, Kevin Gardner, Eliseo Perez-Stable, Anna Napoles-Springer, Susan Neuhausen. Common copy number aberrations in breast cancer in Latinas [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B081.