Page 69 - Read Online

Page 2 of 19 Shi et al. J Cancer Metastasis Treat 2018;4:47 I http://dx.doi.org/10.20517/2394-4722.2018.32

A

B
W (bulk)
S

N

Y

Figure 1. Application of whole exome sequencing (WES) and single-cell sequencing (sc-sequencing) to cancer research. A: Overview
of patient cases to which WES and sc-sequencing were applied to characterize different types of human cancers to understand ITH and
tumor microenvironment. The various types of cancers include liver cancer, lung cancer, renal cell cancer, blood cancer, brain cancer,
breast cancer, pancreatic cancer, colorectal cancer and ovarian cancer compiled from public databases; B: the number of publications
reporting applications of either whole exome or single-cell sequencing to cancer patients within the recent ten years. The key words
“exome/single-cell sequencing” and “cancer patients” were used for searching articles from NCBI

[1-4]
targeted therapies . Next-generation sequencing of bulk tumor tissues from many cancers has generated
an unprecedented amount of multidimensional data bringing in novel insights into mechanisms of tumor
initiation, progression and metastasis [Figure 1]. It has also unmasked the underlying deeper genotypic and
phenotypic heterogeneity that exists between tumors belonging to the same cancer type. The ITH originat-
ing in the cancer genome can be revealed by deep exome and whole genome sequencing. However, tran-
scriptome data from a complex mixture of cells derived from bulk tumor tissues fail to accurately elucidate
the ITH, requiring technologies to study tumors at a single-cell resolution. Over the past ten years, there has
been extraordinary progress in the development and application of single-cell analysis in cancer research
as evidenced by the rise in publications describing different aspects of single-cell sequencing to character-
ize tumors at a deeper level [Figure 1]. In this review, we first introduce the concept of ITH and its clinical
implications. Next, we outline new technologies enabling single-cell analysis with high sensitivity and finally
provide examples of their applications in uncovering new perspectives in cancer diagnostics and treatment.