Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

New England Journal of Medicine, Journal Year: 2012, Volume and Issue: 366(10), P. 883 - 892

Published: March 7, 2012

Intratumor heterogeneity may foster tumor evolution and adaptation hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.

Language: Английский

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The landscape of somatic copy-number alteration across human cancers

Nature, Journal Year: 2010, Volume and Issue: 463(7283), P. 899 - 905

Published: Feb. 1, 2010

Language: Английский

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GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers

Genome biology, Journal Year: 2011, Volume and Issue: 12(4)

Published: April 1, 2011

We describe methods with enhanced power and specificity to identify genes targeted by somatic copy-number alterations (SCNAs) that drive cancer growth. By separating SCNA profiles into underlying arm-level focal alterations, we improve the estimation of background rates for each category. additionally a probabilistic method defining boundaries selected-for regions user-defined confidence. Here detail this revised computational approach, GISTIC2.0, validate its performance in real simulated datasets.

Language: Английский

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Clonal evolution in cancer

Nature, Journal Year: 2012, Volume and Issue: 481(7381), P. 306 - 313

Published: Jan. 1, 2012

Language: Английский

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The causes and consequences of genetic heterogeneity in cancer evolution

Nature, Journal Year: 2013, Volume and Issue: 501(7467), P. 338 - 345

Published: Sept. 17, 2013

Language: Английский

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Intra-tumour heterogeneity: a looking glass for cancer?

Nature reviews. Cancer, Journal Year: 2012, Volume and Issue: 12(5), P. 323 - 334

Published: April 19, 2012

Language: Английский

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Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics

Proceedings of the National Academy of Sciences, Journal Year: 2013, Volume and Issue: 110(10), P. 4009 - 4014

Published: Feb. 14, 2013

Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely key to understanding treatment failure. However, extent as result tumor evolution still poorly understood. To address this, we developed unique surgical multisampling scheme collect spatially distinct fragments from 11 GB patients. We present an integrated genomic analysis uncovers extensive heterogeneity, patients displaying different subtypes within same tumor. Moreover, reconstructed phylogeny for each patient, identifying copy number alterations in EGFR CDKN2A/B/p14ARF early events, aberrations PDGFRA PTEN later events during cancer progression. also characterized clonal organization fragment at single-molecule level, detecting multiple coexisting cell lineages. Our results reveal genome-wide architecture variability across spatial scales patient-specific patterns evolution, consequences design.

Language: Английский

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Models, mechanisms and clinical evidence for cancer dormancy

Nature reviews. Cancer, Journal Year: 2007, Volume and Issue: 7(11), P. 834 - 846

Published: Oct. 24, 2007

Language: Английский

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Tumor heterogeneity: Causes and consequences

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2009, Volume and Issue: 1805(1), P. 105 - 117

Published: Nov. 19, 2009

Language: Английский

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Immune evasion in cancer: Mechanistic basis and therapeutic strategies

Seminars in Cancer Biology, Journal Year: 2015, Volume and Issue: 35, P. S185 - S198

Published: April 5, 2015

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are number of factors that contribute persistence despite having normal host system. Immune editing one the key aspects why tumors surveillance causing lie dormant patients for years through “equilibrium” and “senescence” before re-emerging. In addition, exploit several immunological processes such as targeting regulatory T cell function or their secretions, antigen presentation, modifying production suppressive mediators, tolerance deviation. Besides these, heterogeneity metastasis also play critical role growth. A potential targets like promoting Th1, NK cell, γδ responses, inhibiting Treg functionality, induction IL-12, use drugs including phytochemicals designed counter progression with much success. Some natural agents merit further study. For example, certain polysaccharide components from mushrooms plants shown possess impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. this review, we will discuss advances toward basis cancer summarize efficacy various developed being investigated enhance rejection.

Language: Английский

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