Abstract PL1: Breast Tumor Evolution and Intratumor Heterogeneity - Insights from Single Cell Genomics

Abstract

Breast tumors evolve from single cells in the ducts and acquire mutations leading to divergent lineages and intratumor heterogeneity in invasive cancers. To understand the genomic evolution of breast cancers during complex evolutionary processes including initiation, invasion and therapeutic resistance we have developed single cell sequencing (SCS) methods. I will discuss our efforts in applying SCS methods to study invasion in 10 premalignant breast cancer patients with ductal-carcinoma-in-situ (DCIS), which led to a discovery of early punctuated copy number evolution in the ducts and multi-clonal invasion. I will also discuss our work in applying both single cell DNA and RNA sequencing methods to study chemoresistance evolution in 20 triple-negative breast cancer patients using longitudinal samples, which identified an adaptive genomic evolution and acquired transcriptional reprogramming during resistance. Finally I will present unpublished work on our efforts to develop a 9Human Breast Cell Atlas9 of cell types and cell states (transcriptional programs) of normal cell types, and recent work on delineating copy number evolution in BRCA-positive breast cancer patients. Citation Format: Navin N. Breast Tumor Evolution and Intratumor Heterogeneity - Insights from Single Cell Genomics [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PL1.