crazy-toads.github.io/files/mypubs.bib

@article{jacobs_evolutionary_2014,
	title = {An evolutionary arms race between {KRAB} zinc-finger genes {ZNF}91/93 and {SVA}/{L}1 retrotransposons},
	volume = {516},
	copyright = {© 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
	issn = {0028-0836},
	url = {http://www.nature.com/nature/journal/v516/n7530/full/nature13760.html},
	doi = {10.1038/nature13760},
	abstract = {Throughout evolution primate genomes have been modified by waves of retrotransposon insertions. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, transcriptional silencing of retrotransposons requires KAP1 (also known as TRIM28) and its repressive complex, which can be recruited to target sites by KRAB zinc-finger (KZNF) proteins such as murine-specific ZFP809 which binds to integrated murine leukaemia virus DNA elements and recruits KAP1 to repress them. KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons. However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA) and long interspersed nuclear element 1 (L1), is unknown. Here we show that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8-12 million years ago that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until [sim]12.5 million years ago when the L1PA3-subfamily of retrotransposons escaped ZNF93/'s restriction through the removal of the ZNF93-binding site. Our data support a model where KZNF gene expansion limits the activity of newly emerged retrotransposon classes, and this is followed by mutations in these retrotransposons to evade repression, a cycle of events that could explain the rapid expansion of lineage-specific KZNF genes.},
	language = {en},
	number = {7530},
	urldate = {2015-10-12},
	journal = {Nature},
	author = {Jacobs, Frank M. J. and Greenberg, David and Nguyen, Ngan and Haeussler, Maximilian and Ewing, Adam D. and Katzman, Sol and Paten, Benedict and Salama, Sofie R. and Haussler, David},
	month = dec,
	year = {2014},
	pmid = {25274305},
	keywords = {evolution, interactions, transposon},
	pages = {242--245}
}

@article{trapnell_defining_2015,
	title = {Defining cell types and states with single-cell genomics},
	volume = {25},
	issn = {1088-9051, 1549-5469},
	url = {http://genome.cshlp.org/content/25/10/1491},
	doi = {10.1101/gr.190595.115},
	abstract = {A revolution in cellular measurement technology is under way: For the first time, we have the ability to monitor global gene regulation in thousands of individual cells in a single experiment. Such experiments will allow us to discover new cell types and states and trace their developmental origins. They overcome fundamental limitations inherent in measurements of bulk cell population that have frustrated efforts to resolve cellular states. Single-cell genomics and proteomics enable not only precise characterization of cell state, but also provide a stunningly high-resolution view of transitions between states. These measurements may finally make explicit the metaphor that C.H. Waddington posed nearly 60 years ago to explain cellular plasticity: Cells are residents of a vast “landscape” of possible states, over which they travel during development and in disease. Single-cell technology helps not only locate cells on this landscape, but illuminates the molecular mechanisms that shape the landscape itself. However, single-cell genomics is a field in its infancy, with many experimental and computational advances needed to fully realize its full potential.},
	language = {en},
	number = {10},
	urldate = {2015-10-14},
	journal = {Genome Research},
	author = {Trapnell, Cole},
	month = oct,
	year = {2015},
	pmid = {26430159},
	keywords = {chromatin, evolution, review, single-cell, Waddington},
	pages = {1491--1498}
}

@article{kaufman_zebrafish_2016,
	title = {A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation},
	volume = {351},
	copyright = {Copyright © 2016, American Association for the Advancement of Science},
	issn = {0036-8075, 1095-9203},
	url = {http://science.sciencemag.org/content/351/6272/aad2197},
	doi = {10.1126/science.aad2197},
	abstract = {Visualizing the beginnings of melanoma
In cancer biology, a tumor begins from a single cell within a group of precancerous cells that share genetic mutations. Kaufman et al. used a zebrafish melanoma model to visualize cancer initiation (see the Perspective by Boumahdi and Blanpain). They used a fluorescent reporter that specifically lit up neural crest progenitors that are only present during embryogenesis or during adult melanoma tumor formation. The appearance of this tumor correlated with a set of gene regulatory elements, called super-enhancers, whose identification and manipulation may prove beneficial in detecting and preventing melanoma initiation.
Science, this issue p. 10.1126/science.aad3867; see also p. 453
Structured Abstract
INTRODUCTIONThe “cancerized field” concept posits that cells in a given tissue sharing an oncogenic mutation are cancer-prone, yet only discreet clones within the field initiate tumors. Studying the process of cancer initiation has remained challenging because of (i) the rarity of these events, (ii) the difficulty of visiualizing initiating clones in living organisms, and (iii) the transient nature of a newly transformed clone emerging before it expands to form an early tumor. A more complete understanding of the molecular processes that regulate cancer initiation could provide important prognostic information about which precancerous lesions are most prone to becoming cancer and also implicate druggable molecular pathways that, when inhibited, may prevent the cancer from ever starting.
RATIONALEThe majority of benign nevi carry oncogenic BRAFV600E mutations and can be considered a cancerized field of melanocytes, but they only rarely convert to melanoma. In an effort to define events that initiate cancer, we used a melanoma model in the zebrafish in which the human BRAFV600E oncogene is driven by the melanocyte-specific mitfa promoter. When bred into a p53 mutant background, these fish develop melanoma tumors over the course of many months. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and is specifically reexpressed only in melanoma tumors, making it an ideal candidate for tracking melanoma from initiation onward.
RESULTSWe developed a crestin:EGFP reporter that recapitulates the embryonic neural crest expression pattern of crestin and its expression in melanoma tumors. We show through live imaging of transgenic zebrafish crestin reporters that within a cancerized field (BRAFV600E-mutant; p53-deficient), a single melanocyte reactivates the NCP state, and this establishes that a fate change occurs at melanoma initiation in this model. Early crestin+ patches of cells expand and are transplantable in a manner consistent with their possessing tumorigenic activity, and they exhibit a gene expression pattern consistent with the NCP identity readout by the crestin reporter. The crestin element is regulated by NCP transcription factors, including sox10. Forced sox10 overexpression in melanocytes accelerated melanoma formation, whereas CRISPR/Cas9 targeting of sox10 delayed melanoma onset. We show activation of super-enhancers at NCP genes in both zebrafish and human melanomas, identifying an epigenetic mechanism for control of this NCP signature leading to melanoma.
CONCLUSIONThis work using our zebrafish melanoma model and in vivo reporter of NCP identity allows us to see cancer from its birth as a single cell and shows the importance of NCP-state reemergence as a key event in melanoma initiation from a field of cancer-prone melanocytes. Thus, in addition to the typical fixed genetic alterations in oncogenes and tumor supressors that are required for cancer development, the reemergence of progenitor identity may be an additional rate-limiting step in the formation of melanoma. Preventing NCP reemergence in a field of cancer-prone melanocytes may thus prove therapeutically useful, and the association of NCP genes with super-enhancer regulatory elements implicates the associated druggable epigenetic machinery in this process. Download high-res image Open in new tab Download Powerpoint Neural crest reporter expression in melanoma.The crestin:EGFP transgene is specifically expressed in melanoma in BRAFV600E/p53 mutant melanoma-prone zebrafish. (Top) A single cell expressing crestin:EGFP expands into a small patch of cells over the course of 2 weeks, capturing the initiation of melanoma formation (bracket). (Bottom) A fully formed melanoma specifically expresses crestin:EGFP, whereas the rest of the fish remains EGFP-negative.
The “cancerized field” concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAFV600E mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAFV600E-mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation.
Melanocytes with oncogenic or tumor suppressor mutations revert to expressing the crestin gene early in melanoma formation. [Also see Perspective by Boumahdi and Blanpain]
Melanocytes with oncogenic or tumor suppressor mutations revert to expressing the crestin gene early in melanoma formation. [Also see Perspective by Boumahdi and Blanpain]},
	language = {en},
	number = {6272},
	urldate = {2016-01-29},
	journal = {Science},
	author = {Kaufman, Charles K. and Mosimann, Christian and Fan, Zi Peng and Yang, Song and Thomas, Andrew J. and Ablain, Julien and Tan, Justin L. and Fogley, Rachel D. and Rooijen, Ellen van and Hagedorn, Elliott J. and Ciarlo, Christie and White, Richard M. and Matos, Dominick A. and Puller, Ann-Christin and Santoriello, Cristina and Liao, Eric C. and Young, Richard A. and Zon, Leonard I.},
	month = jan,
	year = {2016},
	pmid = {26823433},
	keywords = {Development, epigenetics, evolution, melanoma, super\_enhancer, zebrafish},
	pages = {aad2197}
}

@article{lipinski_cancer_2016,
	title = {Cancer {Evolution} and the {Limits} of {Predictability} in {Precision} {Cancer} {Medicine}},
	volume = {2},
	issn = {2405-8033},
	url = {http://www.sciencedirect.com/science/article/pii/S2405803315000692},
	doi = {10.1016/j.trecan.2015.11.003},
	abstract = {The ability to predict the future behavior of an individual cancer is crucial for precision cancer medicine. The discovery of extensive intratumor heterogeneity and ongoing clonal adaptation in human tumors substantiated the notion of cancer as an evolutionary process. Random events are inherent in evolution and tumor spatial structures hinder the efficacy of selection, which is the only deterministic evolutionary force. This review outlines how the interaction of these stochastic and deterministic processes, which have been extensively studied in evolutionary biology, limits cancer predictability and develops evolutionary strategies to improve predictions. Understanding and advancing the cancer predictability horizon is crucial to improve precision medicine outcomes.},
	number = {1},
	urldate = {2016-01-30},
	journal = {Trends in Cancer},
	author = {Lipinski, Kamil A. and Barber, Louise J. and Davies, Matthew N. and Ashenden, Matthew and Sottoriva, Andrea and Gerlinger, Marco},
	month = jan,
	year = {2016},
	keywords = {evolution, heterogeneity, resistance, review},
	pages = {49--63}
}

@article{beerenwinkel_computational_2016,
	title = {Computational {Cancer} {Biology}: {An} {Evolutionary} {Perspective}},
	volume = {12},
	shorttitle = {Computational {Cancer} {Biology}},
	url = {http://dx.doi.org/10.1371/journal.pcbi.1004717},
	doi = {10.1371/journal.pcbi.1004717},
	number = {2},
	urldate = {2016-02-05},
	journal = {PLoS Comput Biol},
	author = {Beerenwinkel, Niko and Greenman, Chris D. and Lagergren, Jens},
	month = feb,
	year = {2016},
	keywords = {cancer, concepts, darwinian, epigenetics, evolution, mathematical modeling, review, statistics, variant},
	pages = {e1004717},
	pmid = {26845763}
}