TY - JOUR
T1 - Principles of Reconstructing the Subclonal Architecture of Cancers
AU - Dentro, Stefan C.
AU - Wedge, David C.
AU - Van Loo, Peter
N1 - Publisher Copyright:
Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Most cancers evolve from a single founder cell through a series of clonal expansions that are driven by somatic mutations. These clonal expansions can lead to several coexisting subclones sharing subsets of mutations. Analysis of massively parallel sequencing data can infer a tumor's subclonal composition through the identification of populations of cells with shared mutations. We describe the principles that underlie subclonal reconstruction through single nucleotide variants (SNVs) or copy number alterations (CNAs) from bulk or single-cell sequencing. These principles include estimating the fraction of tumor cells for SNVs and CNAs, performing clustering of SNVs from single- and multisample cases, and single-cell sequencing. The application of subclonal reconstruction methods is providing key insights into tumor evolution, identifying subclonal driver mutations, patterns of parallel evolution and differences in mutational signatures between cellular populations, and characterizing the mechanisms of therapy resistance, spread, and metastasis.
AB - Most cancers evolve from a single founder cell through a series of clonal expansions that are driven by somatic mutations. These clonal expansions can lead to several coexisting subclones sharing subsets of mutations. Analysis of massively parallel sequencing data can infer a tumor's subclonal composition through the identification of populations of cells with shared mutations. We describe the principles that underlie subclonal reconstruction through single nucleotide variants (SNVs) or copy number alterations (CNAs) from bulk or single-cell sequencing. These principles include estimating the fraction of tumor cells for SNVs and CNAs, performing clustering of SNVs from single- and multisample cases, and single-cell sequencing. The application of subclonal reconstruction methods is providing key insights into tumor evolution, identifying subclonal driver mutations, patterns of parallel evolution and differences in mutational signatures between cellular populations, and characterizing the mechanisms of therapy resistance, spread, and metastasis.
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U2 - 10.1101/cshperspect.a026625
DO - 10.1101/cshperspect.a026625
M3 - Review article
C2 - 28270531
AN - SCOPUS:85045870781
SN - 2157-1422
VL - 7
JO - Cold Spring Harbor Perspectives in Medicine
JF - Cold Spring Harbor Perspectives in Medicine
IS - 8
ER -