Single-cell Genomic Copy Number Evolution Reveals Frequent Loss of the Y chromosome in Esophageal Adenocarcinoma
Yin, S.; Zhong, N.; Agrawal, S.; Feng, B.; Pradhan, S.; Jobalia, N. K.; Vaziripour, M.; Poreddy, S. K.; Kresty, L.; Gillaspie, E. A.; Dietz, N. E.; Al-Refaie, W. B.; Nandipati, K. C.; Fu, Y.; Xia, J.
Show abstract
The incidence of esophageal adenocarcinoma (EAC), an aggressive cancer, is rising in Western countries, and incidence is higher in men. To better understand the roles of DNA copy number evolution, tumor heterogeneity, and tumor microenvironment in EAC and its origins, we evaluated EAC, Barretts Esophagus (BE), and normal adjacent tissue using our previously developed ultra-sensitive, single-nucleus DNA copy number analysis (12,186 nuclei, 20 specimens) and single-nucleus RNA-sequencing (snRNA-seq; 87,027 nuclei, 32 specimens). Loss of Y (LOY) chromosome was rare in BE but markedly enriched in EAC. In genome unstable cells, complete LOY chromosome often coincided with X-chromosome duplication. We did not detect X-chromosome inactivation via XIST expression in cells with LOY, suggesting increased expression of X-chromosome genes and potential effects on tumor immune evasion. When considering patients clinical features, we identified distinct differences in tumor microenvironment by sex, age, and obesity status, particularly massively reduced immune cell composition in obese patients. Finally, our cell line models recapitulate LOY, and we identify the first candidate anti-LOY agent. Our findings highlight how LOY affects tumor subpopulations and shapes the tumor microenvironment during EAC progression.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Aberrant cell state plasticity mediated by developmental reprogramming precedescolorectal cancer initiation 95%
- Aneuploidy and deregulated DNA damage response define haploinsufficiency in breast tissues of BRCA2 mutation carriers 95%
- Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS-chemokine-myeloid axis 94%
Similar papers in this journal
Similar papers in this journal
- Single cell genomic characterization reveals the cellular reprogramming of the gastric tumor microenvironment 96%
- Myeloid cell-associated resistance to PD-1/PD-L1 blockade in urothelial cancer revealed through bulk and single-cell RNA sequencing 95%
- The genomic landscape of early stage ovarian high grade serous carcinoma 95%
Similar papers in this journal
- Detection and monitoring of translocation renal cell carcinoma via plasma cell-free epigenomic profiling 95%
- The cholesterol biosynthesis enzyme FAXDC2 couples Wnt/beta-catenin to RTK/MAPK signaling 94%
- NF2 loss malignantly transforms human pancreatic acinar cells and enhances cell fitness under environmental stress 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.