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Shi et al. J Cancer Metastasis Treat 2018;4:47 Journal of Cancer
DOI: 10.20517/2394-4722.2018.32 Metastasis and Treatment

Review Open Access

Unmasking tumor heterogeneity and clonal
evolution by single-cell analysis

Xiaoshan Shi, Papia Chakraborty, Amitabha Chaudhuri

MedGenome Inc., Foster City, California 94404, USA.
Correspondence to: Dr. Amitabha Chaudhuri, MedGenome Inc., Foster City, California 94404, USA.
E-mail: amitc@medgenome.com

How to cite this article: Shi X, Chakraborty P, Chaudhuri A. Unmasking tumor heterogeneity and clonal evolution by single-cell
analysis. J Cancer Metastasis Treat 2018;4:47. http://dx.doi.org/10.20517/2394-4722.2018.32

Received: 24 May 2018 First Decision: 17 Jul 2018 Revised: 24 Jul 2018 Accepted: 9 Aug 2018 Published: 31 Aug 2018
Science Editors: Yi-Hong Zhou Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
The intratumoral heterogeneity orchestrated by the tumor intrinsic and extrinsic mechanisms enable cancers to
persist and spread notwithstanding the use of aggressive interventional therapies. The heterogeneity is revealed at
multiple levels - at the level of individual tumor cells, in the cellular composition of tumor infiltrates and in the chemical
microenvironment in which the cells reside. Deconvoluting the complex nature of the cell types present in the tumor,
along with the homo and heterotypic interactions between different cell types can produce novel insights of biological
and clinical relevance. However, most techniques analyze tumors at a gross level missing key inter-cell-type genotypic
and phenotypic differences. The advent of single-cell sequencing has given an unprecedented opportunity to analyze
the tumor at a resolution that not only captures the diversity of the cellular composition of a tumor but also provides
information on the genetic, epigenetic and functional states of different cell types. In this review, we summarize the
genesis of tumor heterogeneity, its impact on tumor growth and progression and their clinical consequences. We
present an overview of the currently available platforms for isolation and sequencing of single tumor cells and provide
evidence of its utility in precision medicine and personalized therapy.

Keywords: Intratumoral heterogeneity, single-cell sequencing, clonal evolution, circulating tumor cells, drug resistance

INTRODUCTION
A single cell is the ultimate denominator of a multicellular organism. In the progression of cancer, a single
cell begins its journey to evolve into a malignant tumor cell and forms distinct subpopulations leading to
intratumoral heterogeneity (ITH). Clonal diversity, the source of ITH, is the characteristics of all cancers
and plays a critical role in cancer invasion, metastasis and development of resistance to targeted and non-

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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