Early events during neoplastic progression in Barrett's esophagus

Reid, Brian J.

doi:10.3233/cbm-2011-0162

Cited by 17 publications

(16 citation statements)

References 158 publications

(175 reference statements)

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“…Many of these changes have also been associated with a markedly increased risk of progression to dysplasia or EAC 19, 30, 31 . Specifically, loss or mutation of TP53 and CDKN2A , aneuploidy and the extent of clonal diversity observed in IM are all generally accepted biomarkers for increased risk of progression 3, 19, 24 . In contrast, only one study has specifically analyzed DNA changes in NGM 25 .…”

Section: Discussionmentioning

confidence: 99%

“…One thing that is known however, is that EAC arises through accumulation of multiple DNA alterations (mutation, DNA copy number abnormality, methylation), many of which are also observed in early dysplastic lesions 19-21 . Furthermore, IM contains frequent alterations in known cancer-associated genes ( TP53, CDKN2A, FHIT, WWOX ) 20, 22, 23 and these DNA alterations are presumably the underlying cause for the increased cancer risk associated with IM 24 . On the other hand, very little is known about DNA alterations in NGM with ploidy changes being the only possible aberrations noted to date 25 .…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Cancer-Associated Genetic Abnormalities in Columnar-Lined Esophagus Tissues With and Without Goblet Cells

Bandla¹,

Peters²,

Ruff³

et al. 2014

Annals of Surgery

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Objective To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells. Background Barrett’s esophagus (BE) is associated with increased risk of esophageal adenocarcinoma (EAC) but the appropriate histologic definition of BE is debated. Intestinal metaplasia (IM) is defined by the presence of goblet cells while non-goblet cell metaplasia (NGM) lacks goblet cells. Both have been implicated in EAC risk but this is controversial. While IM is known to harbor genetic changes associated with EAC, little is known about NGM. We hypothesized that if NGM and IM infer similar EAC risk then they would harbor similar genetic aberrations in genes associated with EAC. Methods Ninety frozen NGM, IM, and normal tissues from 45 subjects were studied. DNA copy number abnormalities (CNA’s) were identified using microarrays and fluorescence in situ hybridization (FISH). Targeted sequencing of all exons from twenty EAC-associated genes was performed on metaplasia biopsies using Ion AmpliSeq™ DNA sequencing. Results Frequent CNA’s targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In one subject, FISH confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy. Targeted sequencing revealed 11 non-synonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples. Conclusions This study reports the largest and most comprehensive comparison of DNA aberrations in IM and NGM genomes. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of Cancer-Associated Genetic Abnormalities in Columnar-Lined Esophagus Tissues With and Without Goblet Cells

Bandla¹,

Peters²,

Ruff³

et al. 2014

Annals of Surgery

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“…Whereas abnormalities in telomere length occur at an early stage in the development of epithelial carcinogenesis (58), CIN and tetraploidy are early events in cervical carcinogenesis (59). In addition, tetraploidy may be a predictive marker for progression of Barrett's esophagus into esophageal adenocarcinoma (60). Researchers have also proposed that tetraploidy, much like aneuploidy (61), may stimulate tumor formation (62).…”

Section: Cin In Precursor Lesionsmentioning

confidence: 99%

Chromosomal Instability in Tumor Initiation and Development

2019

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Chromosomal instability (CIN) is one of the major forms of genomic instability in various human cancers and is recognized as a common hallmark of tumorigenesis and heterogeneity. However, some malignant tumors show a paucity of chromosomal alterations, suggesting that tumor progression and evolution can occur in the absence of CIN. It is unclear whether CIN is stable between precursor lesions, primary tumor, and metastases or if it evolves during these steps. In this review, we describe the influence of CIN on the various steps in tumor initiation and development. Given the recognized significant effects of CIN in cancer, CIN-targeted therapeutics could have a major impact on improving clinical outcomes.

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“…TP53 , the gene for p53, is a well-known tumor suppressor gene that is frequently lost early in BE through mutation or loss of heterozygosity (LOH) [55]. TP53 LOH has been shown to identify a subset of BE patients who are at risk for progression to EAC [56, 57].…”

Section: Discussionmentioning

confidence: 99%

Global DNA methylation patterns in Barrett’s esophagus, dysplastic Barrett’s, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use

et al. 2016

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BackgroundThe risk of developing Barrett’s esophagus (BE) and/or esophageal adenocarcinoma (EAC) is associated with specific demographic and behavioral factors, including gender, obesity/elevated body mass index (BMI), and tobacco use. Alterations in DNA methylation, an epigenetic modification that can affect gene expression and that can be influenced by environmental factors, is frequently present in both BE and EAC and is believed to play a role in the formation of BE and its progression to EAC. It is currently unknown whether obesity or tobacco smoking influences the risk of developing BE/EAC via the induction of alterations in DNA methylation. To investigate this possibility, we assessed the genome-wide methylation status of 81 esophageal tissues, including BE, dysplastic BE, and EAC epithelia using HumanMethylation450 BeadChips (Illumina).ResultsWe found numerous differentially methylated loci in the esophagus tissues when comparing males to females, obese to lean individuals, and smokers to nonsmokers. Differences in DNA methylation between these groups were seen in a variety of functional genomic regions and both within and outside of CpG islands. Several cancer-related pathways were found to have differentially methylated genes between these comparison groups.ConclusionsOur findings suggest obesity and tobacco smoking may influence DNA methylation in the esophagus and raise the possibility that these risk factors affect the development of BE, dysplastic BE, and EAC through influencing the epigenetic status of specific loci that have a biologically plausible role in cancer formation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0273-7) contains supplementary material, which is available to authorized users.

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Early events during neoplastic progression in Barrett's esophagus

Cited by 17 publications

References 158 publications

Comparison of Cancer-Associated Genetic Abnormalities in Columnar-Lined Esophagus Tissues With and Without Goblet Cells

Comparison of Cancer-Associated Genetic Abnormalities in Columnar-Lined Esophagus Tissues With and Without Goblet Cells

Chromosomal Instability in Tumor Initiation and Development

Global DNA methylation patterns in Barrett’s esophagus, dysplastic Barrett’s, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use

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