Current Progresses of Single Cell DNA Sequencing in Breast Cancer Research

Abstract

Breast cancers display striking genetic and phenotypic diversities. To date, several hypotheses are raised to explain and understand the heterogeneity, including theories for cancer stem cell (CSC) and clonal evolution. According to the CSC theory, the most tumorigenic cells, while maintaining themselves through symmetric division, divide asymmetrically to generate non-CSCs with less tumorigenic and metastatic potential, although they can also dedifferentiate back to CSCs. Clonal evolution theory recapitulates that a tumor initially arises from a single cell, which then undergoes clonal expansion to a population of cancer cells. During tumorigenesis and evolution process, cancer cells undergo different degrees of genetic instability and consequently obtain varied genetic aberrations. Yet the heterogeneity in breast cancers is very complex, poorly understood and subjected to further investigation. In recent years, single cell sequencing (SCS) technology developed rapidly, providing a powerful new way to better understand the heterogeneity, which may lay foundations to some new strategies for breast cancer therapies. In this review, we will summarize development of SCS technologies and recent advances of SCS in breast cancer.

Keywords: Breast cancer; Cancer stem cells; Intertumor heterogeneity; Intratumor heterogeneity; Single cell sequencing..

Figure 1

CSC model. Normal stem cells can undergo oncogenic transformation to give rise to cancer stem cells (CSCs). CSCs can generate CSCs and non-CSC through symmetric division and asymmetric division, respectively, driving tumor growth and seeding metastases. On the other hand, non-CSCs can also dedifferentiate back to CSCs under stimuli from microenvironment. CSCs to non-CSCs is bidirectional and dynamic conversion, leading to great diversity within tumors.

Figure 2

Clonal evolution model. Tumor can evolve through clonal expansion of cancer cell, giving rise to heterogeneity within tumors, which is created by genetic changes. Under selection pressure, earlier diver mutations (red color), and new driver mutations (yellow color) obtain advantage for outgrowth of clones and drive tumors grow.