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Published in: Clinical and Translational Medicine 1/2017

Open Access 01-12-2017 | Review

Single-cell sequencing and tumorigenesis: improved understanding of tumor evolution and metastasis

Authors: Darrell L. Ellsworth, Heather L. Blackburn, Craig D. Shriver, Shahrooz Rabizadeh, Patrick Soon-Shiong, Rachel E. Ellsworth

Published in: Clinical and Translational Medicine | Issue 1/2017

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Abstract

Extensive genomic and transcriptomic heterogeneity in human cancer often negatively impacts treatment efficacy and survival, thus posing a significant ongoing challenge for modern treatment regimens. State-of-the-art DNA- and RNA-sequencing methods now provide high-resolution genomic and gene expression portraits of individual cells, facilitating the study of complex molecular heterogeneity in cancer. Important developments in single-cell sequencing (SCS) technologies over the past 5 years provide numerous advantages over traditional sequencing methods for understanding the complexity of carcinogenesis, but significant hurdles must be overcome before SCS can be clinically useful. In this review, we: (1) highlight current methodologies and recent technological advances for isolating single cells, single-cell whole-genome and whole-transcriptome amplification using minute amounts of nucleic acids, and SCS, (2) summarize research investigating molecular heterogeneity at the genomic and transcriptomic levels and how this heterogeneity affects clonal evolution and metastasis, and (3) discuss the promise for integrating SCS in the clinical care arena for improved patient care.
Literature
1.
go back to reference Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F et al (2013) An estimationof the number of cells in the human body. Ann Hum Biol 40:463–471CrossRefPubMed Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F et al (2013) An estimationof the number of cells in the human body. Ann Hum Biol 40:463–471CrossRefPubMed
2.
go back to reference Gajecka M (2016) Unrevealed mosaicism in the next-generation sequencing era. Mol Genet Genomics 291:513–530CrossRefPubMed Gajecka M (2016) Unrevealed mosaicism in the next-generation sequencing era. Mol Genet Genomics 291:513–530CrossRefPubMed
3.
go back to reference Allison KH, Sledge GW (2014) Heterogeneity and cancer. Oncology (Williston Park). 28:772–778PubMed Allison KH, Sledge GW (2014) Heterogeneity and cancer. Oncology (Williston Park). 28:772–778PubMed
4.
go back to reference Gawad C, Koh W, Quake SR (2016) Single-cell genome sequencing: current state of the science. Nat Rev Genet 17:175–188CrossRefPubMed Gawad C, Koh W, Quake SR (2016) Single-cell genome sequencing: current state of the science. Nat Rev Genet 17:175–188CrossRefPubMed
5.
go back to reference Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N et al (2009) mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods 6:377–382CrossRefPubMed Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N et al (2009) mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods 6:377–382CrossRefPubMed
6.
8.
go back to reference Liang J, Cai W, Sun Z (2014) Single-cell sequencing technologies: current and future. J Genet Genom 41:513–528CrossRef Liang J, Cai W, Sun Z (2014) Single-cell sequencing technologies: current and future. J Genet Genom 41:513–528CrossRef
9.
go back to reference Kolodziejczyk AA, Kim JK, Svensson V, Marioni JC, Teichmann SA (2015) The technology and biology of single-cell RNA sequencing. Mol Cell 58:610–620CrossRefPubMed Kolodziejczyk AA, Kim JK, Svensson V, Marioni JC, Teichmann SA (2015) The technology and biology of single-cell RNA sequencing. Mol Cell 58:610–620CrossRefPubMed
10.
go back to reference Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904CrossRefPubMed Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C et al (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904CrossRefPubMed
11.
go back to reference Talasaz AH, Powell AA, Huber DE, Berbee JG, Roh KH, Yu W et al (2009) Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci USA 106:3970–3975CrossRefPubMedPubMedCentral Talasaz AH, Powell AA, Huber DE, Berbee JG, Roh KH, Yu W et al (2009) Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc Natl Acad Sci USA 106:3970–3975CrossRefPubMedPubMedCentral
12.
go back to reference Fabbri F, Carloni S, Zoli W, Ulivi P, Gallerani G, Fici P et al (2013) Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs. Cancer Lett 335:225–231CrossRefPubMed Fabbri F, Carloni S, Zoli W, Ulivi P, Gallerani G, Fici P et al (2013) Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs. Cancer Lett 335:225–231CrossRefPubMed
13.
go back to reference Choi JH, Ogunniyi AO, Du M, Du M, Kretschmann M, Eberhardt J et al (2010) Development and optimization of a process for automated recovery of single cells identified by microengraving. Biotechnol Prog 26:888–895CrossRefPubMed Choi JH, Ogunniyi AO, Du M, Du M, Kretschmann M, Eberhardt J et al (2010) Development and optimization of a process for automated recovery of single cells identified by microengraving. Biotechnol Prog 26:888–895CrossRefPubMed
14.
go back to reference Adams DL, Stefansson S, Haudenschild C, Martin SS, Charpentier M, Chumsri S et al (2015) Cytometric characterization of circulating tumor cells captured by microfiltration and their correlation to the Cell Search(®) CTC test. Cytometry A 87:137–144CrossRefPubMed Adams DL, Stefansson S, Haudenschild C, Martin SS, Charpentier M, Chumsri S et al (2015) Cytometric characterization of circulating tumor cells captured by microfiltration and their correlation to the Cell Search(®) CTC test. Cytometry A 87:137–144CrossRefPubMed
15.
go back to reference Huang L, Ma F, Chapman A, Lu S, Xie XS (2015) Single-cell whole-genome amplification and sequencing: methodology and applications. Annu Rev Genom Hum Genet 16:79–102CrossRef Huang L, Ma F, Chapman A, Lu S, Xie XS (2015) Single-cell whole-genome amplification and sequencing: methodology and applications. Annu Rev Genom Hum Genet 16:79–102CrossRef
17.
go back to reference Ye B, Gao Q, Zeng Z, Stary CM, Jian Z, Xiong X et al (2016) Single-cell sequencing technology in oncology: applications for clinical therapies and research. Anal Cell Pathol (Amst) 2016:9369240 Ye B, Gao Q, Zeng Z, Stary CM, Jian Z, Xiong X et al (2016) Single-cell sequencing technology in oncology: applications for clinical therapies and research. Anal Cell Pathol (Amst) 2016:9369240
18.
go back to reference Arneson N, Hughes S, Houlston R, Done S (2008) Whole-genome amplification by degenerate oligonucleotide primed PCR (DOP-PCR). CSH Protoc. 2008:pdb.prot4919PubMed Arneson N, Hughes S, Houlston R, Done S (2008) Whole-genome amplification by degenerate oligonucleotide primed PCR (DOP-PCR). CSH Protoc. 2008:pdb.prot4919PubMed
19.
go back to reference Dean FB, Hosono S, Fang L, Wu X, Faruqi AF, Bray-Ward P et al (2002) Comprehensive human genome amplification using multiple displacement amplification. Proc Natl Acad Sci USA 99:5261–5266CrossRefPubMedPubMedCentral Dean FB, Hosono S, Fang L, Wu X, Faruqi AF, Bray-Ward P et al (2002) Comprehensive human genome amplification using multiple displacement amplification. Proc Natl Acad Sci USA 99:5261–5266CrossRefPubMedPubMedCentral
20.
go back to reference Zong C, Lu S, Chapman AR, Xie XS (2012) Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338:1622–1626CrossRefPubMedPubMedCentral Zong C, Lu S, Chapman AR, Xie XS (2012) Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338:1622–1626CrossRefPubMedPubMedCentral
21.
go back to reference Picelli S, Björklund ÅK, Faridani OR, Sagasser S, Winberg G, Sandberg R (2013) Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat Methods 10:1096–1098CrossRefPubMed Picelli S, Björklund ÅK, Faridani OR, Sagasser S, Winberg G, Sandberg R (2013) Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat Methods 10:1096–1098CrossRefPubMed
22.
go back to reference Ramsköld D, Luo S, Wang YC, Li R, Deng Q, Faridani OR et al (2012) Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nat Biotechnol 30:777–782CrossRefPubMedPubMedCentral Ramsköld D, Luo S, Wang YC, Li R, Deng Q, Faridani OR et al (2012) Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nat Biotechnol 30:777–782CrossRefPubMedPubMedCentral
23.
go back to reference Sasagawa Y, Nikaido I, Hayashi T, Danno H, Uno KD, Imai T et al (2013) Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity. Genome Biol 14:R31CrossRefPubMedPubMedCentral Sasagawa Y, Nikaido I, Hayashi T, Danno H, Uno KD, Imai T et al (2013) Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity. Genome Biol 14:R31CrossRefPubMedPubMedCentral
24.
go back to reference Hashimshony T, Wagner F, Sher N, Yanai I (2012) CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. Cell Rep 2:666–673CrossRefPubMed Hashimshony T, Wagner F, Sher N, Yanai I (2012) CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. Cell Rep 2:666–673CrossRefPubMed
25.
go back to reference Hashimshony T, Senderovich N, Avital G, Klochendler A, de Leeuw Y, Anavy L et al (2016) CEL-Seq2: sensitive highly-multiplexed single-cell RNA-Seq. Genome Biol 17:77CrossRefPubMedPubMedCentral Hashimshony T, Senderovich N, Avital G, Klochendler A, de Leeuw Y, Anavy L et al (2016) CEL-Seq2: sensitive highly-multiplexed single-cell RNA-Seq. Genome Biol 17:77CrossRefPubMedPubMedCentral
26.
go back to reference Islam S, Kjällquist U, Moliner A, Zajac P, Fan JB, Lönnerberg P et al (2012) Highly multiplexed and strand-specific single-cell RNA 5′-end sequencing. Nat Protoc 7:813–828CrossRefPubMed Islam S, Kjällquist U, Moliner A, Zajac P, Fan JB, Lönnerberg P et al (2012) Highly multiplexed and strand-specific single-cell RNA 5′-end sequencing. Nat Protoc 7:813–828CrossRefPubMed
28.
go back to reference Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF (2004) Therapeutic implications of cancer stem cells. Curr Opin Genet Dev 14:43–47CrossRefPubMed Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF (2004) Therapeutic implications of cancer stem cells. Curr Opin Genet Dev 14:43–47CrossRefPubMed
29.
30.
go back to reference Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS (2003) Stem cells in normal breast development and breast cancer. Cell Prolif 36(Suppl 1):59–72CrossRefPubMed Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS (2003) Stem cells in normal breast development and breast cancer. Cell Prolif 36(Suppl 1):59–72CrossRefPubMed
31.
go back to reference Yang Z, Li C, Fan Z, Liu H, Zhang X, Cai Z et al (2017) Single-cell sequencing reveals variants in ARID1A, GPRC5A and MLL2 driving self-renewal of human bladder cancer stem cells. Eur Urol 71:8–12CrossRefPubMed Yang Z, Li C, Fan Z, Liu H, Zhang X, Cai Z et al (2017) Single-cell sequencing reveals variants in ARID1A, GPRC5A and MLL2 driving self-renewal of human bladder cancer stem cells. Eur Urol 71:8–12CrossRefPubMed
32.
go back to reference Boesch M, Sopper S, Zeimet AG, Reimer D, Gastl G, Ludewig B et al (2016) Heterogeneity of cancer stem cells: rationale for targeting the stem cell niche. Biochim Biophys Acta 1866:276–289PubMed Boesch M, Sopper S, Zeimet AG, Reimer D, Gastl G, Ludewig B et al (2016) Heterogeneity of cancer stem cells: rationale for targeting the stem cell niche. Biochim Biophys Acta 1866:276–289PubMed
33.
go back to reference Liu N, Liu L, Pan X (2014) Single-cell analysis of the transcriptome and its application in the characterization of stem cells and early embryos. Cell Mol Life Sci 71:2707–2715CrossRefPubMed Liu N, Liu L, Pan X (2014) Single-cell analysis of the transcriptome and its application in the characterization of stem cells and early embryos. Cell Mol Life Sci 71:2707–2715CrossRefPubMed
35.
go back to reference Akrap N, Andersson D, Bom E, Gregersson P, Ståhlberg A, Landberg G (2016) Identification of distinct breast cancer stem cell populations based on single-cell analyses of functionally enriched stem and progenitor pools. Stem Cell Rep 6:121–136CrossRef Akrap N, Andersson D, Bom E, Gregersson P, Ståhlberg A, Landberg G (2016) Identification of distinct breast cancer stem cell populations based on single-cell analyses of functionally enriched stem and progenitor pools. Stem Cell Rep 6:121–136CrossRef
36.
go back to reference Lawson DA, Bhakta NR, Kessenbrock K, Prummel KD, Yu Y, Takai K et al (2015) Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature 526:131–135CrossRefPubMedPubMedCentral Lawson DA, Bhakta NR, Kessenbrock K, Prummel KD, Yu Y, Takai K et al (2015) Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature 526:131–135CrossRefPubMedPubMedCentral
37.
go back to reference Lei B, Zhang XY, Zhou JP, Mu GN, Li YW, Zhang YX et al (2016) Transcriptome sequencing of HER2-positive breast cancer stem cells identifies potential prognostic marker. Tumour Biol 37:14757–14764CrossRefPubMed Lei B, Zhang XY, Zhou JP, Mu GN, Li YW, Zhang YX et al (2016) Transcriptome sequencing of HER2-positive breast cancer stem cells identifies potential prognostic marker. Tumour Biol 37:14757–14764CrossRefPubMed
38.
go back to reference Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H et al (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344:1396–1401CrossRefPubMedPubMedCentral Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H et al (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344:1396–1401CrossRefPubMedPubMedCentral
39.
go back to reference Wang Y, Waters J, Leung ML, Unruh A, Roh W, Shi X et al (2014) Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature 512:155–160CrossRefPubMedPubMedCentral Wang Y, Waters J, Leung ML, Unruh A, Roh W, Shi X et al (2014) Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature 512:155–160CrossRefPubMedPubMedCentral
40.
go back to reference Gao R, Davis A, McDonald TO, Sei E, Shi X, Wang Y et al (2016) Punctuated copy number evolution and clonal stasis in triple-negative breast cancer. Nat Genet 48:1119–1130CrossRefPubMedPubMedCentral Gao R, Davis A, McDonald TO, Sei E, Shi X, Wang Y et al (2016) Punctuated copy number evolution and clonal stasis in triple-negative breast cancer. Nat Genet 48:1119–1130CrossRefPubMedPubMedCentral
41.
go back to reference Baslan T, Kendall J, Ward B, Cox H, Leotta A, Rodgers L et al (2015) Optimizing sparse sequencing of single cells for highly multiplex copy number profiling. Genome Res 25:714–724CrossRefPubMedPubMedCentral Baslan T, Kendall J, Ward B, Cox H, Leotta A, Rodgers L et al (2015) Optimizing sparse sequencing of single cells for highly multiplex copy number profiling. Genome Res 25:714–724CrossRefPubMedPubMedCentral
42.
go back to reference Nguyen A, Yoshida M, Goodarzi H, Tavazoie SF (2016) Highly variable cancer subpopulations that exhibit enhanced transcriptome variability and metastatic fitness. Nat Commun 7:11246CrossRefPubMedPubMedCentral Nguyen A, Yoshida M, Goodarzi H, Tavazoie SF (2016) Highly variable cancer subpopulations that exhibit enhanced transcriptome variability and metastatic fitness. Nat Commun 7:11246CrossRefPubMedPubMedCentral
43.
go back to reference Lee MC, Lopez-Diaz FJ, Khan SY, Tariq MA, Dayn Y, Vaske CJ et al (2014) Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing. Proc Natl Acad Sci USA. 111:E4726–E4735CrossRefPubMedPubMedCentral Lee MC, Lopez-Diaz FJ, Khan SY, Tariq MA, Dayn Y, Vaske CJ et al (2014) Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing. Proc Natl Acad Sci USA. 111:E4726–E4735CrossRefPubMedPubMedCentral
44.
go back to reference Min JW, Kim WJ, Han JA, Jung YJ, Kim KT, Park WY et al (2015) Identification of distinct tumor subpopulations in lung adenocarcinoma via single-cell RNA-seq. PLoS ONE 10:e0135817CrossRefPubMedPubMedCentral Min JW, Kim WJ, Han JA, Jung YJ, Kim KT, Park WY et al (2015) Identification of distinct tumor subpopulations in lung adenocarcinoma via single-cell RNA-seq. PLoS ONE 10:e0135817CrossRefPubMedPubMedCentral
45.
go back to reference Kim KT, Lee HW, Lee HO, Kim SC, Seo YJ, Chung W et al (2015) Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells. Genome Biol 16:127CrossRefPubMedPubMedCentral Kim KT, Lee HW, Lee HO, Kim SC, Seo YJ, Chung W et al (2015) Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells. Genome Biol 16:127CrossRefPubMedPubMedCentral
46.
go back to reference Suzuki A, Matsushima K, Makinoshima H, Sugano S, Kohno T, Tsuchihara K et al (2015) Single-cell analysis of lung adenocarcinoma cell lines reveals diverse expression patterns of individual cells invoked by a molecular target drug treatment. Genome Biol 16:66CrossRefPubMedPubMedCentral Suzuki A, Matsushima K, Makinoshima H, Sugano S, Kohno T, Tsuchihara K et al (2015) Single-cell analysis of lung adenocarcinoma cell lines reveals diverse expression patterns of individual cells invoked by a molecular target drug treatment. Genome Biol 16:66CrossRefPubMedPubMedCentral
47.
go back to reference Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS et al (2014) Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomark Prev 23:1985–1996CrossRef Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS et al (2014) Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomark Prev 23:1985–1996CrossRef
48.
go back to reference Francis JM, Zhang CZ, Maire CL, Jung J, Manzo VE, Adalsteinsson VA et al (2014) EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov 4:956–971CrossRefPubMedPubMedCentral Francis JM, Zhang CZ, Maire CL, Jung J, Manzo VE, Adalsteinsson VA et al (2014) EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov 4:956–971CrossRefPubMedPubMedCentral
49.
go back to reference Yu C, Yu J, Yao X, Wu WK, Lu Y, Tang S et al (2014) Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing. Cell Res 24:701–712CrossRefPubMedPubMedCentral Yu C, Yu J, Yao X, Wu WK, Lu Y, Tang S et al (2014) Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing. Cell Res 24:701–712CrossRefPubMedPubMedCentral
50.
51.
go back to reference Li Y, Xu X, Song L, Hou Y, Li Z, Tsang S et al (2012) Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer. Gigascience 1:12CrossRefPubMedPubMedCentral Li Y, Xu X, Song L, Hou Y, Li Z, Tsang S et al (2012) Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer. Gigascience 1:12CrossRefPubMedPubMedCentral
52.
go back to reference Zhang X, Zhang M, Hou Y, Xu L, Li W, Zou Z et al (2016) Single-cell analyses of transcriptional heterogeneity in squamous cell carcinoma of urinary bladder. Oncotarget 7:66069–66076PubMedPubMedCentral Zhang X, Zhang M, Hou Y, Xu L, Li W, Zou Z et al (2016) Single-cell analyses of transcriptional heterogeneity in squamous cell carcinoma of urinary bladder. Oncotarget 7:66069–66076PubMedPubMedCentral
53.
go back to reference Xu X, Hou Y, Yin X, Bao L, Tang A, Song L et al (2012) Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell 148:886–895CrossRefPubMed Xu X, Hou Y, Yin X, Bao L, Tang A, Song L et al (2012) Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell 148:886–895CrossRefPubMed
54.
go back to reference Kim KT, Lee HW, Lee HO, Song HJ, da Jeong E, Shin S et al (2016) Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma. Genome Biol 17:80CrossRefPubMedPubMedCentral Kim KT, Lee HW, Lee HO, Song HJ, da Jeong E, Shin S et al (2016) Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma. Genome Biol 17:80CrossRefPubMedPubMedCentral
55.
go back to reference Hughes AE, Magrini V, Demeter R, Miller CA, Fulton R, Fulton LL et al (2014) Clonal architecture of secondary acute myeloid leukemia defined by single-cell sequencing. PLoS Genet 10:e1004462CrossRefPubMedPubMedCentral Hughes AE, Magrini V, Demeter R, Miller CA, Fulton R, Fulton LL et al (2014) Clonal architecture of secondary acute myeloid leukemia defined by single-cell sequencing. PLoS Genet 10:e1004462CrossRefPubMedPubMedCentral
56.
go back to reference Gawad C, Koh W, Quake SR (2014) Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics. Proc Natl Acad Sci USA 111:17947–17952CrossRefPubMedPubMedCentral Gawad C, Koh W, Quake SR (2014) Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics. Proc Natl Acad Sci USA 111:17947–17952CrossRefPubMedPubMedCentral
57.
go back to reference Bakker B, Taudt A, Belderbos ME, Porubsky D, Spierings DC, de Jong TV et al (2016) Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies. Genome Biol 17:115CrossRefPubMedPubMedCentral Bakker B, Taudt A, Belderbos ME, Porubsky D, Spierings DC, de Jong TV et al (2016) Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies. Genome Biol 17:115CrossRefPubMedPubMedCentral
58.
go back to reference Hou Y, Song L, Zhu P, Zhang B, Tao Y, Xu X et al (2012) Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm. Cell 148:873–885CrossRefPubMed Hou Y, Song L, Zhu P, Zhang B, Tao Y, Xu X et al (2012) Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm. Cell 148:873–885CrossRefPubMed
59.
go back to reference Luo M, Clouthier SG, Deol Y, Liu S, Nagrath S, Azizi E et al (2015) Breast cancer stem cells: current advances and clinical implications. Methods Mol Biol 1293:1–49CrossRefPubMed Luo M, Clouthier SG, Deol Y, Liu S, Nagrath S, Azizi E et al (2015) Breast cancer stem cells: current advances and clinical implications. Methods Mol Biol 1293:1–49CrossRefPubMed
60.
go back to reference Fehm T, Sagalowsky A, Clifford E, Beitsch P, Saboorian H, Euhus D et al (2002) Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res 8:2073–2084PubMed Fehm T, Sagalowsky A, Clifford E, Beitsch P, Saboorian H, Euhus D et al (2002) Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant. Clin Cancer Res 8:2073–2084PubMed
61.
go back to reference Lv Q, Gong L, Zhang T, Ye J, Chai L, Ni C et al (2016) Prognostic value of circulating tumor cells in metastatic breast cancer: a systemic review and meta-analysis. Clin Transl Oncol 18:322–330CrossRefPubMed Lv Q, Gong L, Zhang T, Ye J, Chai L, Ni C et al (2016) Prognostic value of circulating tumor cells in metastatic breast cancer: a systemic review and meta-analysis. Clin Transl Oncol 18:322–330CrossRefPubMed
62.
go back to reference Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Jückstock J et al (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse-a European pooled analysis. Clin Cancer Res 17:2967–2976CrossRefPubMed Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Jückstock J et al (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse-a European pooled analysis. Clin Cancer Res 17:2967–2976CrossRefPubMed
63.
go back to reference Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S (2009) Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res 11:R46CrossRefPubMedPubMedCentral Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S (2009) Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res 11:R46CrossRefPubMedPubMedCentral
64.
go back to reference Yang MH, Imrali A, Heeschen C (2015) Circulating cancer stem cells: the importance to select. Chin J Cancer Res 27:437–449PubMedPubMedCentral Yang MH, Imrali A, Heeschen C (2015) Circulating cancer stem cells: the importance to select. Chin J Cancer Res 27:437–449PubMedPubMedCentral
65.
go back to reference Ellsworth RE, Blackburn HL, Shriver CD, Soon-Shiong P, Ellsworth DL. Molecular heterogeneity in breast cancer: state of the science and implications for patient care. Semin Cell Dev Biol. 2016 (in press) Ellsworth RE, Blackburn HL, Shriver CD, Soon-Shiong P, Ellsworth DL. Molecular heterogeneity in breast cancer: state of the science and implications for patient care. Semin Cell Dev Biol. 2016 (in press)
66.
go back to reference Qian M, Wang DC, Chen H, Cheng Y. Detection of single cell heterogeneity in cancer. Semin Cell Dev Biol. 2016 (in press) Qian M, Wang DC, Chen H, Cheng Y. Detection of single cell heterogeneity in cancer. Semin Cell Dev Biol. 2016 (in press)
67.
go back to reference Heitzer E, Auer M, Gasch C, Pichler M, Ulz P, Hoffmann EM et al (2013) Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res 73:2965–2975CrossRefPubMed Heitzer E, Auer M, Gasch C, Pichler M, Ulz P, Hoffmann EM et al (2013) Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res 73:2965–2975CrossRefPubMed
68.
go back to reference Ni X, Zhuo M, Su Z, Duan J, Gao Y, Wang Z et al (2013) Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci USA 110:21083–21088CrossRefPubMedPubMedCentral Ni X, Zhuo M, Su Z, Duan J, Gao Y, Wang Z et al (2013) Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci USA 110:21083–21088CrossRefPubMedPubMedCentral
69.
go back to reference Jiang R, Lu YT, Ho H, Li B, Chen JF, Lin M et al (2015) A comparison of isolated circulating tumor cells and tissue biopsies using whole-genome sequencing in prostate cancer. Oncotarget. 6:44781–44793PubMedPubMedCentral Jiang R, Lu YT, Ho H, Li B, Chen JF, Lin M et al (2015) A comparison of isolated circulating tumor cells and tissue biopsies using whole-genome sequencing in prostate cancer. Oncotarget. 6:44781–44793PubMedPubMedCentral
70.
go back to reference Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P et al (2014) Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol 32:479–484CrossRefPubMedPubMedCentral Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P et al (2014) Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol 32:479–484CrossRefPubMedPubMedCentral
71.
go back to reference De Luca F, Rotunno G, Salvianti F, Galardi F, Pestrin M, Gabellini S et al (2016) Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer. Oncotarget 7:26107–26119PubMedPubMedCentral De Luca F, Rotunno G, Salvianti F, Galardi F, Pestrin M, Gabellini S et al (2016) Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer. Oncotarget 7:26107–26119PubMedPubMedCentral
72.
go back to reference Pestrin M, Salvianti F, Galardi F, De Luca F, Turner N, Malorni L et al (2015) Heterogeneity of PIK3CA mutational status at the single cell level in circulating tumor cells from metastatic breast cancer patients. Mol Oncol. 9:749–757CrossRefPubMed Pestrin M, Salvianti F, Galardi F, De Luca F, Turner N, Malorni L et al (2015) Heterogeneity of PIK3CA mutational status at the single cell level in circulating tumor cells from metastatic breast cancer patients. Mol Oncol. 9:749–757CrossRefPubMed
73.
go back to reference Fernandez SV, Bingham C, Fittipaldi P, Austin L, Palazzo J, Palmer G et al (2014) TP53 mutations detected in circulating tumor cells present in the blood of metastatic triple negative breast cancer patients. Breast Cancer Res 16:445CrossRefPubMedPubMedCentral Fernandez SV, Bingham C, Fittipaldi P, Austin L, Palazzo J, Palmer G et al (2014) TP53 mutations detected in circulating tumor cells present in the blood of metastatic triple negative breast cancer patients. Breast Cancer Res 16:445CrossRefPubMedPubMedCentral
74.
go back to reference Deng G, Krishnakumar S, Powell AA, Zhang H, Mindrinos MN, Telli ML et al (2014) Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow. BMC Cancer 14:456CrossRefPubMedPubMedCentral Deng G, Krishnakumar S, Powell AA, Zhang H, Mindrinos MN, Telli ML et al (2014) Single cell mutational analysis of PIK3CA in circulating tumor cells and metastases in breast cancer reveals heterogeneity, discordance, and mutation persistence in cultured disseminated tumor cells from bone marrow. BMC Cancer 14:456CrossRefPubMedPubMedCentral
75.
go back to reference Jordan NV, Bardia A, Wittner BS, Benes C, Ligorio M, Zheng Y et al (2016) HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature 537:102–106CrossRefPubMedPubMedCentral Jordan NV, Bardia A, Wittner BS, Benes C, Ligorio M, Zheng Y et al (2016) HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature 537:102–106CrossRefPubMedPubMedCentral
76.
go back to reference Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G et al (2012) Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS ONE 7:e33788CrossRefPubMedPubMedCentral Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G et al (2012) Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS ONE 7:e33788CrossRefPubMedPubMedCentral
77.
go back to reference Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT et al (2015) RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 349:1351–1356CrossRefPubMedPubMedCentral Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT et al (2015) RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 349:1351–1356CrossRefPubMedPubMedCentral
78.
go back to reference Ting DT, Wittner BS, Ligorio M, Vincent Jordan N, Shah AM, Miyamoto DT et al (2014) Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep. 8:1905–1918CrossRefPubMedPubMedCentral Ting DT, Wittner BS, Ligorio M, Vincent Jordan N, Shah AM, Miyamoto DT et al (2014) Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep. 8:1905–1918CrossRefPubMedPubMedCentral
79.
go back to reference Wiedswang G, Borgen E, Kåresen R, Kvalheim G, Nesland JM, Qvist H et al (2003) Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 21:3469–3478CrossRefPubMed Wiedswang G, Borgen E, Kåresen R, Kvalheim G, Nesland JM, Qvist H et al (2003) Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 21:3469–3478CrossRefPubMed
80.
go back to reference Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802CrossRefPubMed Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802CrossRefPubMed
81.
go back to reference Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G et al (2006) Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 12:5615–5621CrossRefPubMed Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G et al (2006) Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 12:5615–5621CrossRefPubMed
82.
go back to reference Møller EK, Kumar P, Voet T, Peterson A, Van Loo P, Mathiesen RR et al (2013) Next-generation sequencing of disseminated tumor cells. Front Oncol. 3:320CrossRefPubMedPubMedCentral Møller EK, Kumar P, Voet T, Peterson A, Van Loo P, Mathiesen RR et al (2013) Next-generation sequencing of disseminated tumor cells. Front Oncol. 3:320CrossRefPubMedPubMedCentral
83.
go back to reference Fehm T, Müller V, Aktas B, Janni W, Schneeweiss A, Stickeler E et al (2010) HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat 124:403–412CrossRefPubMed Fehm T, Müller V, Aktas B, Janni W, Schneeweiss A, Stickeler E et al (2010) HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat 124:403–412CrossRefPubMed
84.
go back to reference Carpenter EL, Rader J, Ruden J, Rappaport EF, Hunter KN, Hallberg PL et al (2014) Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells. Front Oncol. 4:201CrossRefPubMedPubMedCentral Carpenter EL, Rader J, Ruden J, Rappaport EF, Hunter KN, Hallberg PL et al (2014) Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells. Front Oncol. 4:201CrossRefPubMedPubMedCentral
85.
go back to reference Demeulemeester J, Kumar P, Møller EK, Nord S, Wedge DC, Peterson A et al (2016) Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing. Genome Biol 17:250CrossRefPubMedPubMedCentral Demeulemeester J, Kumar P, Møller EK, Nord S, Wedge DC, Peterson A et al (2016) Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing. Genome Biol 17:250CrossRefPubMedPubMedCentral
87.
go back to reference Burrell RA, McGranahan N, Bartek J, Swanton C (2013) The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501:338–345CrossRefPubMed Burrell RA, McGranahan N, Bartek J, Swanton C (2013) The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501:338–345CrossRefPubMed
88.
go back to reference Aparicio S, Caldas C (2013) The implications of clonal genome evolution for cancer medicine. N Engl J Med 368:842–851CrossRefPubMed Aparicio S, Caldas C (2013) The implications of clonal genome evolution for cancer medicine. N Engl J Med 368:842–851CrossRefPubMed
89.
90.
go back to reference Mato Prado M, Frampton AE, Stebbing J, Krell J (2016) Single-cell sequencing in cancer research. Expert Rev Mol Diagn. 16:1–5CrossRefPubMed Mato Prado M, Frampton AE, Stebbing J, Krell J (2016) Single-cell sequencing in cancer research. Expert Rev Mol Diagn. 16:1–5CrossRefPubMed
91.
go back to reference Dervan AP, Deverka PA, Trosman JR, Weldon CB, Douglas MP, Phillips KA. Payer decision making for next-generation sequencing-based genetic tests: insights from cell-free DNA prenatal screening. Genet Med. 2016 (in press) Dervan AP, Deverka PA, Trosman JR, Weldon CB, Douglas MP, Phillips KA. Payer decision making for next-generation sequencing-based genetic tests: insights from cell-free DNA prenatal screening. Genet Med. 2016 (in press)
92.
go back to reference Niu F, Wang DC, Lu J, Wu W, Wang X (2016) Potentials of single-cell biology in identification and validation of disease biomarkers. J Cell Mol Med 20:1789–1795CrossRefPubMedPubMedCentral Niu F, Wang DC, Lu J, Wu W, Wang X (2016) Potentials of single-cell biology in identification and validation of disease biomarkers. J Cell Mol Med 20:1789–1795CrossRefPubMedPubMedCentral
93.
go back to reference Blackburn HL, Schroeder B, Turner C, Shriver CD, Ellsworth DL, Ellsworth RE (2015) Management of incidental findings in the era of next-generation sequencing. Curr Genomics 16:159–174CrossRefPubMedPubMedCentral Blackburn HL, Schroeder B, Turner C, Shriver CD, Ellsworth DL, Ellsworth RE (2015) Management of incidental findings in the era of next-generation sequencing. Curr Genomics 16:159–174CrossRefPubMedPubMedCentral
94.
go back to reference Laskin J, Jones S, Aparicio S, Chia S, Ch’ng C, Deyell R et al (2015) Lessons learned from the application of whole-genome analysis to the treatment of patients with advanced cancers. Cold Spring Harb Mol Case Stud. 1:a000570CrossRefPubMedPubMedCentral Laskin J, Jones S, Aparicio S, Chia S, Ch’ng C, Deyell R et al (2015) Lessons learned from the application of whole-genome analysis to the treatment of patients with advanced cancers. Cold Spring Harb Mol Case Stud. 1:a000570CrossRefPubMedPubMedCentral
95.
go back to reference Chantrill LA, Nagrial AM, Watson C, Johns AL, Martyn-Smith M, Simpson S et al (2015) Precision medicine for advanced pancreas cancer: the individualized molecular pancreatic cancer therapy (IMPaCT) trial. Clin Cancer Res 21:2029–2037CrossRefPubMed Chantrill LA, Nagrial AM, Watson C, Johns AL, Martyn-Smith M, Simpson S et al (2015) Precision medicine for advanced pancreas cancer: the individualized molecular pancreatic cancer therapy (IMPaCT) trial. Clin Cancer Res 21:2029–2037CrossRefPubMed
96.
go back to reference Dey SS, Kester L, Spanjaard B, Bienko M, van Oudenaarden A (2015) Integrated genome and transcriptome sequencing of the same cell. Nat Biotechnol 33:285–289CrossRefPubMedPubMedCentral Dey SS, Kester L, Spanjaard B, Bienko M, van Oudenaarden A (2015) Integrated genome and transcriptome sequencing of the same cell. Nat Biotechnol 33:285–289CrossRefPubMedPubMedCentral
97.
go back to reference Macaulay IC, Teng MJ, Haerty W, Kumar P, Ponting CP, Voet T (2016) Separation and parallel sequencing of the genomes and transcriptomes of single cells using G&T-seq. Nat Protoc 11:2081–2103CrossRefPubMed Macaulay IC, Teng MJ, Haerty W, Kumar P, Ponting CP, Voet T (2016) Separation and parallel sequencing of the genomes and transcriptomes of single cells using G&T-seq. Nat Protoc 11:2081–2103CrossRefPubMed
98.
go back to reference Hou Y, Guo H, Cao C, Li X, Hu B, Zhu P et al (2016) Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. Cell Res 26:304–319CrossRefPubMedPubMedCentral Hou Y, Guo H, Cao C, Li X, Hu B, Zhu P et al (2016) Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. Cell Res 26:304–319CrossRefPubMedPubMedCentral
99.
go back to reference Darmanis S, Gallant CJ, Marinescu VD, Niklasson M, Segerman A, Flamourakis G et al (2016) Simultaneous multiplexed measurement of RNA and proteins in single cells. Cell Rep. 14:380–389CrossRefPubMed Darmanis S, Gallant CJ, Marinescu VD, Niklasson M, Segerman A, Flamourakis G et al (2016) Simultaneous multiplexed measurement of RNA and proteins in single cells. Cell Rep. 14:380–389CrossRefPubMed
100.
go back to reference Lee JH, Daugharthy ER, Scheiman J, Kalhor R, Yang JL, Ferrante TC et al (2014) Highly multiplexed subcellular RNA sequencing in situ. Science 343:1360–1363CrossRefPubMedPubMedCentral Lee JH, Daugharthy ER, Scheiman J, Kalhor R, Yang JL, Ferrante TC et al (2014) Highly multiplexed subcellular RNA sequencing in situ. Science 343:1360–1363CrossRefPubMedPubMedCentral
Metadata
Title
Single-cell sequencing and tumorigenesis: improved understanding of tumor evolution and metastasis
Authors
Darrell L. Ellsworth
Heather L. Blackburn
Craig D. Shriver
Shahrooz Rabizadeh
Patrick Soon-Shiong
Rachel E. Ellsworth
Publication date
01-12-2017
Publisher
Springer Berlin Heidelberg
Published in
Clinical and Translational Medicine / Issue 1/2017
Electronic ISSN: 2001-1326
DOI
https://doi.org/10.1186/s40169-017-0145-6

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