Genetic clonal diversity predicts progression to esophageal adenocarcinoma

Maley, Carlo C.; Galipeau, Patricia C.; Finley, Jennifer C.; Wongsurawat, V. Jon; Li, Xiaohong; Sanchez, Carissa A.; Paulson, Thomas G.; Blount, Patricia L.; Risques, Rosa Ana; Rabinovitch, Peter S.; Reid, Brian J.

doi:10.1038/ng1768

Cited by 641 publications

(639 citation statements)

References 26 publications

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“…Given the limitations of endoscopic surveillance and histologic dysplasia as a risk stratifi cation tool, molecular markers to identify patients at increased risk for progression have been studied. Abnormalities including DNA content abnormalities, chromosomal abnormalities, gene mutations, methylation changes, and clonal diversity measurements defi ne patients at increased risk for progression to cancer (128)(129)(130)(131)(132). Th ese genetic abnormalities appear to occur early in disease development ( 133 ).…”

Section: Advanced Endoscopic Imaging Techniquesmentioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,336

1,412

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Recent population studies suggest that gastroesophageal refl ux disease (GERD) is increasing in prevalence, both in the United States and worldwide ( 1,2 ). Th e diagnosis of GERD is associated with a 10-15% risk of Barrett's esophagus (BE), a change of the normal squamous epithelium of the distal esophagus to a columnar-lined intestinal metaplasia (IM). Risk factors associated with the development of BE include long-standing GERD, male gender, central obesity ( 3 ), and age over 50 years ( 4,5 ). Th e goal of a screening and surveillance program for BE is to identify individuals at risk for progression to esophageal adenocarcinoma (EAC), a malignancy that has been increasing in incidence since the 1970s ( 6,7 ).Th e purpose of this guideline is to review the defi nition and epidemiology of BE, available screening modalities for BE detection, rationale and methods for surveillance, and available treatment modalities including medical, endoscopic, and surgical techniques. In order to evaluate the level of evidence and strength of recommendations, we used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system ( 8 ). Th e level of evidence ranged from "high" (implying that further research was unlikely to change the authors' confi dence in the estimate of the eff ect) to "moderate" (further research would be likely to have an impact on the confi dence in the estimate of eff ect) to "low" (further research would be expected to have an important impact on the confi dence in the estimate of the eff ect and would be likely to change the estimate) or "very low" (any estimate of eff ect is very uncertain). Th e strength of a recommendation was graded as "strong" when the desirable eff ects of an intervention clearly outweighed the undesirable eff ects and as "conditional" when there was uncertainty about the tradeoff s. We used meta-analyses or systematic reviews when available, followed by clinical trials and cohort and case-control studies. In order to determine the level Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring for these patients. These guidelines continue to endorse screening of high-risk patients for BE; however, routine screening is limited to men with refl ux symptoms and multiple other risk factors. Acknowledging recent data on the low risk of malignant progression in patients with nondysplastic BE, endoscopic surveillance intervals are attenuated in this population; patients with nondysplastic BE should undergo endoscopic surveillance no more frequently than every 3-5 years. Neither routine use of biomarker panels nor advanced endoscopic imaging techniques (beyond high-defi nition endoscopy) is recommended at this time. Endoscopic ablative therapy is recommended for patients with BE and high-grade dysplasia, as well as T1a esophageal adenocarcinoma. Based on recent level 1 evidence, endoscopic ablative therapy is ...

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Section: Advanced Endoscopic Imaging Techniquesmentioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,336

1,412

View full text Add to dashboard Cite

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“…Intra-tumor heterogeneity, the coexistence of different clones within a tumor, is commonly observed [Greenman et al 2007, Navin et al 2011 and has implications for cancer progression, diagnosis, and treatment [Dexter & Leith 1986, Maley et al 2006, Almendro et al 2013]. Why such heterogeneity exists remains unclear [Merlo et al 2006, Almendro et al 2013, because clones that have a proliferative advantage within the tumour are expected to drive other subclones to extinction.…”

Section: Implications For Cancer Researchmentioning

confidence: 99%

Cooperation among cancer cells as public goods games on Voronoi networks

Archetti

2016

Journal of Theoretical Biology

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Cancer cells produce growth factors that diffuse and sustain tumor proliferation, a form of cooperation among cancer cells that can be studied using mathematical models of public goods in the framework of evolutionary game theory. Cell populations, however, form heterogeneous networks that cannot be described by regular lattices or scale-free networks, the types of graphs generally used in the study of cooperation. To describe the dynamics of growth factor production in populations of cancer cells, I study public goods games on Voronoi networks, using a range of non-linear benefits that account for the known properties of growth factors, and different types of diffusion gradients. The results are surprisingly similar to those obtained on regular graphs and different from results on scale-free networks, revealing that network heterogeneity per se does not promote cooperation when public goods diffuse beyond one-step neighbours. The exact shape of the diffusion gradient is not crucial, however, whereas the type of non-linear benefit is an essential determinant of the dynamics. Public goods games on Voronoi networks can shed light on intra-tumor heterogeneity, the evolution of resistance to therapies that target growth factors, and new types of cell therapy.

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“…Similar features of chromosomal instability and population heterogeneity were observed, for example, in cancer cells by creating and propagating minor genetic variants that can outgrow the majority under specific conditions (Maley et al. 2006; Sipos et al. 2014).…”

Section: Discussionmentioning

confidence: 99%

Constitutive aneuploidy and genomic instability in the single‐celled eukaryote Giardia intestinalis

et al. 2016

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Giardia intestinalis is an important single‐celled human pathogen. Interestingly, this organism has two equal‐sized transcriptionally active nuclei, each considered diploid. By evaluating condensed chromosome numbers and visualizing homologous chromosomes by fluorescent in situ hybridization, we determined that the Giardia cells are constitutively aneuploid. We observed karyotype inter‐and intra‐population heterogeneity in eight cell lines from two clinical isolates, suggesting constant karyotype evolution during in vitro cultivation. High levels of chromosomal instability and frequent mitotic missegregations observed in four cell lines correlated with a proliferative disadvantage and growth retardation. Other cell lines, although derived from the same clinical isolate, revealed a stable yet aneuploid karyotype. We suggest that both chromatid missegregations and structural rearrangements contribute to shaping the Giardia genome, leading to whole‐chromosome aneuploidy, unequal gene distribution, and a genomic divergence of the two nuclei within one cell. Aneuploidy in Giardia is further propagated without p53‐mediated cell cycle arrest and might have been a key mechanism in generating the genetic diversity of this human pathogen.

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Genetic clonal diversity predicts progression to esophageal adenocarcinoma

Cited by 641 publications

References 26 publications

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Cooperation among cancer cells as public goods games on Voronoi networks

Constitutive aneuploidy and genomic instability in the single‐celled eukaryote Giardia intestinalis

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