4.8 Article

Molecular phenotyping reveals the identity of Barrett's esophagus and its malignant transition

Journal

SCIENCE
Volume 373, Issue 6556, Pages 760-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abd1449

Keywords

-

Funding

  1. Medical Research Council [RG84369]
  2. CRUK [C9545/A29580, RG66287, RG81771/84119]
  3. Wellcome Trust [206194]
  4. Chan Zuckerberg Initiative [174169]
  5. NIHR Cambridge BRC [RG92051]
  6. Chan Zuckerberg Initiative Award
  7. Cambridge Cancer Centre Clinical Research Fellowship
  8. CRUK

Ask authors/readers for more resources

This study revealed that Barrett's esophagus originates from the gastric cardia through specific transcriptional programs. Esophageal adenocarcinoma likely arises from undifferentiated Barrett's esophagus cell types, even in the absence of a clearly identifiable metaplastic precursor. This finding has important implications for early cancer detection strategies.
The origin of human metaplastic states and their propensity for cancer is poorly understood. Barrett's esophagus is a common metaplastic condition that increases the risk for esophageal adenocarcinoma, and its cellular origin is enigmatic. To address this, we harvested tissues spanning the gastroesophageal junction from healthy and diseased donors, including isolation of esophageal submucosal glands. A combination of single-cell transcriptomic profiling, in silico lineage tracing from methylation, open chromatin and somatic mutation analyses, and functional studies in organoid models showed that Barrett's esophagus originates from gastric cardia through c-MYC and HNF4A-driven transcriptional programs. Furthermore, our data indicate that esophageal adenocarcinoma likely arises from undifferentiated Barrett's esophagus cell types even in the absence of a pathologically identifiable metaplastic precursor, illuminating early detection strategies.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available