One patient, two lesions, two oncogenic drivers of gastric cancer.
Bottom Line: Deep-sequencing of a primary tumor and metastasis from a single patient, and functional validation in culture, reveals that TGFBR2 and FGFR2 act as drivers of gastric cancer.
Deep-sequencing of a primary tumor and metastasis from a single patient, and functional validation in culture, reveals that TGFBR2 and FGFR2 act as drivers of gastric cancer.
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Mentions: So what do the mutations identified in the tumors from this gastric cancer patient actually tell us (Figure 1)? First, as a germline CDH1 mutation was found, it tells us that an early chapter in the story was loss of the wild-type allele of this gene, probably coinciding with biallelic loss of the TP53 gene (encoding cellular tumor antigen p53) or preceding it. Thus, mutation of CDH1 and TP53 are early events that probably drove tumor initiation and set the ball rolling. But why does the metastasis lack the FGFR2 amplification? This is most likely explained by the early dissemination of tumor cells from the primary lesion, which was removed by gastrectomy at presentation, to the metastatic site in the ovary, with these cells lying dormant, only to be reanimated years later by loss of TGFBR2. An alternative scenario could be that loss of TGFBR2 helped a cancer cell transit from the primary tumor to the metastatic site, where it lay in wait - either way, distal dissemination of the tumor must have been an early event occurring before removal of the primary.Figure 1