Abstract
The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.
Highlights
The role of focal amplifications and extrachromosomal DNA is unknown in gastric cardia adenocarcinoma (GCA)
We found that GCA shares some common oncogene focal amplifications with both gastric cancer and esophageal cancer including CCNE1, EGFR, and MYC (Supplementary Fig. 3)
We found that the frequency of chromothripsis in GCA patients was quite diverse across the cohort, where the range of chromothripsis was from 0 to 4 for high confidence (HC) and 0 to 14 for
Summary
The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC) occur together in the Taihang Mountains of north central China at high rates[18,19,20]. Gastric cancer in this area occurs primarily in the uppermost portion of the stomach and is referred to as GCA, and those in the remainder of the stomach are called gastric noncardia adenocarcinoma (GNCA)[21]. A previous study reported that oncogene amplification and gene rearrangements drive the progression and poor prognosis of GCA29 It is still unclear whether focal amplifications and ecDNA is present in GCA, and what role they play in the GCA progression or whether it is correlated with patient prognosis. We identify the focal amplifications and ecDNA amplicons present in most GCA patients, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated
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