Published in:
01-05-2020 | Metastasis | Original Article—Liver, Pancreas, and Biliary Tract
Multi-regional sequencing reveals clonal and polyclonal seeding from primary tumor to metastases in advanced gastric cancer
Published in: Journal of Gastroenterology | Issue 5/2020
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Background
Tumor metastases to lymph nodes and distant organs are associated with worse prognosis in gastric cancer. However, little is known about the genetic profiles, subclonal architecture, and evolutional processes across primary tumors and metastases.
Methods
We analyzed the genetic alterations of 106 multiregional samples including primary tumors, lymph node metastases, and visceral metastases from 10 patients with advanced gastric cancer. Histologically different portions were obtained by laser-capture microdissection. We reconstructed the subclonal architectures and inferred the primary to lymph or visceral metastatic seeding patterns.
Results
The different histological portions in primary tumors had common mutations, suggesting common ancestral tumor origins transformed into distinct histological types. In almost all cases, TP53 mutations were identified as clonal mutations across primary tumors and metastases. Subclonal reconstruction and phylogenetic analysis showed primary tumors were classified into monoclonal or polyclonal tumors. All monoclonal primary tumors disseminated as metastases with the same tumor composition (100%, 26/26 samples). In contrast, polyclonal primary tumors mainly spread as metastases by way of polyclonal seeding (84%: 37/44 samples).
Conclusions
Clonal mutations were maintained at both the primary and metastatic sites and genetic divergence of these was low. These findings shed light on the genetic basis of primary tumor dissemination and metastatic processes in advanced gastric cancer.