The first five years of single-cell cancer genomics and beyond

Abstract

Single-cell sequencing (SCS) is a powerful new tool for investigating evolution and diversity in cancer and understanding the role of rare cells in tumor progression. These methods have begun to unravel key questions in cancer biology that have been difficult to address with bulk tumor measurements. Over the past five years, there has been extraordinary progress in technological developments and research applications, but these efforts represent only the tip of the iceberg. In the coming years, SCS will greatly improve our understanding of invasion, metastasis, and therapy resistance during cancer progression. These tools will also have direct translational applications in the clinic, in areas such as early detection, noninvasive monitoring, and guiding targeted therapy. In this perspective, I discuss the progress that has been made and the myriad of unexplored applications that still lie ahead in cancer research and medicine.

Next-generation Sequencing (NGS) Analysis on Single Circulating Tumor Cells (CTCs) with No Need of Whole-genome Amplification (WGA)

“…Moreover, the presence of some specific sequence variants in driver genes is currently under intensive investigation for cancer molecular diagnosis and pharmacogenomics including prediction of either susceptibility or resistance to the targeted therapy (5)(6)(7). In this context, introduction of innovative biotechnologies allows to identify, recover and analyze CTCs from the peripheral blood to perform the so-called "liquid biopsy" procedure (8)(9)(10)(11)(12)(13)(14)(15)(16).…”

Microdevices for Non-Invasive Detection of Bladder Cancer

“…In particular, the ability to computationally cluster data from related cell populations could provide an in silico method to isolate data from rare exfoliated tumor cells (as compared to contaminant urothelial cells) [133][134][135] and could also indicate distinct subpopulations of cancerous cells that would likely benefit from treatment with a coordinated, concerted panel of drugs informed by knowledge of the characteristics of individual cells [136][137][138]. More broadly, application of single-cell transcriptomics to exfoliated bladder cancer cells from a large population of patients would provide a reference transcriptomic dataset of bladder cancer variants, useful for placing patients within a broader context of prior knowledge and for predicting efficacy of potential treatment paths based on historical data [139].…”

De nouveaux types cellulaires identifiés par séquençage haut débit sur cellule unique

“…Par reductio ad absurdum 1 [10,11] ou tumoral, contribuant au concept d'hétérogénéité intra-tumorale [12]. Elles ont égale-ment permis la reconstruction de la généalogie des cellules cancéreuses, par l'accumulation de mutations au gré des divisions cellulaires, et du processus de dissémination métastatique, étayant au niveau moléculaire, le concept clinique d'histoire naturelle de la maladie [13]. À l'avenir, cette approche pourrait permettre de déceler une hétérogé-néité fonctionnelle au sein de cellules indiscernables jusque là.…”