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Barrett's esophagus (BE) is the link between one of the most common gastrointestinal diseases, gastroesophageal reflux disease (GERD) and the most rapidly increasing cancer of the GI tract. The clinical importance of Barrett's esophagus is that it is a premalignant lesion for esophageal adenocarcinoma (EAC). Barrett's esophagus was first described by Norman Barrett in 1950 as gastric epithelium lining the lower part of the anatomical esophagus. The historical belief was that the presence of columnar epithelium for the last 2–3 cm of the distal esophagus was a normal finding. Thus, pathologic Barrett's esophagus was initially described as a columnar lined esophagus (CLE) for greater than 3 cm proximal to the gastroesophageal junction (GEJ). The current definition, widely accepted in North America, is the endoscopic appearance of columnar epithelium in the tubular esophagus and a biopsy demonstrating specialized intestinal metaplasia (SIM) on histological examination. SIM is itself characterized by the presence of goblet cells and is considered the hallmark lesion of Barrett's esophagus because it is known to predispose to the development of dysplasia and, therefore, adenocarcinoma regardless of the location in the esophagus.
Unlike the well-characterized sequence of genetic alterations that lead to some forms of colon cancer, no well-defined pathway has been shown to mediate the pathogenesis of adenocarcinoma in Barrett's esophagus. There is considerable genetic heterogeneity among the adenocarcinomas that develop in patients with Barrett's esophagus, which frequently involve alterations in tumor suppressor genes. A number of the many molecular changes that have been described in Barrett's-associated cancers are so-called “hitchhiker mutations” that do not directly contribute to carcinogenesis but are retained in the cancer cell genome because they are linked to oncogenic mutations.
Multiple genetic changes are detectable in Barrett's esophagus. Whole-genome studies have demonstrated that the majority of Barrett's esophagus samples show some level of chromosomal instability, as characterized by copy number gains, copy number losses, and the loss of heterozygosity (LOH). These changes increase in frequency and size as the condition progresses, with single nucleotide polymorphism (SNP) array analyses suggesting that genomic abnormalities increase from involving less than 2% of the genome in early-stage Barrett's metaplasia to over 30% in late-stage Barrett's esophagus. The most frequent change seen is the loss of the short arm of chromosome 9, including 9p21.3 (CDKN2A/p16). Other common abnormalities in early-stage Barrett's esophagus include copy loss on 3p across the FHIT gene locus (3p59.8–60.6) and 16q, across the WWOX locus (16q77.3). A variety of somatic genetic alterations usually associated with cancer, including the loss of p53, adenomatous polyposis coli (APC), and Rb (retinoblastoma protein), and the overexpression of cyclin D1, Bcl2, and SRC kinase, are also readily detectable in Barrett's metaplasia tissue. However, there is little evidence that these events have a direct role in the development of Barrett's esophagus itself, and, likely, many are early events in the progression of Barrett's metaplasia to dysplasia and EAC.
It is not clear which of the many genetic changes described in Barrett's esophagus are required for oncogenesis; when these are identified, they might be used in the diagnosis and as therapeutic targets. Creative Biogene, as a leading biotechnology company, can offer various Barrett's esophagus pathway-related products including stable cell lines, viral particles and clones for your pathogenesis study and drug discovery projects.