Assessment of esophageal adenocarcinoma risk using somatic chromosome alterations in longitudinal samples in Barrett's esophagus.

Publication Type:

Journal Article


Cancer prevention research (Philadelphia, Pa.), Volume 8, Issue 9, p.845-856 (2015)


Genomics Core Facility, Specimen Processing Core Facility


Cancers detected at a late stage are often refractory to treatments and ultimately lethal. Early detection can significantly increase survival probability, but attempts to reduce mortality by early detection have frequently increased overdiagnosis of indolent conditions that do not progress over a lifetime. Study designs that incorporate biomarker trajectories in time and space are needed to distinguish patients who progress to an early cancer from those who follow an indolent course. Esophageal adenocarcinoma (EA) is characterized by evolution of punctuated and catastrophic somatic chromosomal alterations and high levels of overall mutations but few recurrently mutated genes aside from TP53. Endoscopic surveillance of Barrett's esophagus (BE) for early cancer detection provides an opportunity for assessment of alterations for cancer risk in patients who progress to EA compared to nonprogressors. We investigated 1,272 longitudinally collected esophageal biopsies in a 248 Barrett's patient case-cohort study with 20,425 person-months of follow-up, including 79 who progressed to early-stage EA. Cancer progression risk was assessed for total chromosomal alterations, diversity, and chromosomal region-specific alterations measured with single nucleotide polymorphism arrays in biopsies obtained over esophageal space and time. A model using 29 chromosomal features was developed for cancer risk prediction (Area under receiver operator curve=0.94). The model prediction performance was robust in two independent EA sets and outperformed TP53 mutation, flow cytometric DNA content and histopathologic diagnosis of dysplasia. This study offers a strategy to reduce overdiagnosis in BE and improve early detection of EA and potentially other cancers characterized by punctuated and catastrophic chromosomal evolution.