The Combination of Genetic Instability and Clonal Expansion Predicts Progression to Esophageal Adenocarcinomaстатья из журнала
Аннотация: Abstract There is debate in the literature over the relative importance of genetic instability and clonal expansion during progression to cancer. Barrett’s esophagus is a uniquely suited model to investigate neoplastic progression prospectively because periodic endoscopic biopsy surveillance is recommended for early detection of esophageal adenocarcinoma. We hypothesized that expansion of clones with genetic instability would predict progression to esophageal adenocarcinoma. We measured p16 (CDKN2A/INK4A) lesions (loss of heterozygosity, mutations, and CpG island methylation), p53 (TP53) lesions (loss of heterozygosity, mutation) and ploidy abnormalities (aneuploidy, tetraploidy) within each Barrett’s esophagus segment of a cohort of 267 research participants, who were followed prospectively with cancer as an outcome. We defined the size of a lesion as the fraction of cells with the lesion multiplied by the length of the Barrett’s esophagus segment. A Cox proportional hazards regression indicates that the sizes of clones with p53 loss of heterozygosity (relative risk = 1.27x for an x cm clone; 95% confidence interval, 1.07–1.50) or ploidy abnormalities (relative risk = 1.31x for an x cm clone; 95% confidence interval, 1.07–1.60) predict progression to esophageal adenocarcinoma better than the mere presence of such clones (likelihood ratio test, P < 0.01). Controlling for length of the Barrett’s esophagus segment had little effect. The size of a clone with a p16 lesion is not a significant predictor of esophageal adenocarcinoma when we controlled for p53 loss of heterozygosity status. The combination of clonal expansion and genetic instability is a better predictor of cancer outcome than either alone. This implies that interventions that limit expansion of genetically unstable clones may reduce risk of progression to cancer.
Год издания: 2004
Авторы: Carlo C. Maley, Patricia C. Galipeau, Xiaohong Li, Carissa A. Sanchez, Thomas G. Paulson, Patricia L. Blount, Brian J. Reid
Издательство: American Association for Cancer Research
Источник: Cancer Research
Ключевые слова: Pancreatic and Hepatic Oncology Research, Genetic factors in colorectal cancer, Esophageal Cancer Research and Treatment
Другие ссылки: Cancer Research (PDF)
Cancer Research (HTML)
PubMed (HTML)
Cancer Research (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 64
Выпуск: 20
Страницы: 7629–7633