Details

Autor(en) / Beteiligte

• Nowicki-Osuch, Karol
• Zhuang, Lizhe
• Jammula, Sriganesh
• Bleaney, Christopher W
• Mahbubani, Krishnaa T
• Devonshire, Ginny
• Katz-Summercorn, Annalise
• Eling, Nils
• Wilbrey-Clark, Anna
• Madissoon, Elo
• Gamble, John
• Di Pietro, Massimiliano
• O'Donovan, Maria
• Meyer, Kerstin B
• Saeb-Parsy, Kourosh
• Sharrocks, Andrew D
• Teichmann, Sarah A
• Marioni, John C
• Fitzgerald, Rebecca C

Titel

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

Ist Teil von

• Science (American Association for the Advancement of Science), 2021-08, Vol.373 (6556), p.760-767

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2021

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.