The stomach is an organ unique in its function, environment and exposures. How does this affect the mutations that normal cells in the stomach acquire? What does this reveal about the origins of stomach cancer? These questions and more in our @nature.com paper: www.nature.com/articles/s41... - ThreadSky

timcoorens.bsky.social • 7 days ago

The stomach is an organ unique in its function, environment and exposures. How does this affect the mutations that normal cells in the stomach acquire? What does this reveal about the origins of stomach cancer? These questions and more in our @nature.com paper:
https://www.nature.com/articles/s41586-025-08708-6

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timcoorens.bsky.social•7 days ago

The lining of the stomach produces acid, and is the origin of stomach cancer, with many risk factors (diet, smoking, H. pylori infection). We used LCM to isolate and sequence normal stomach glands, from gastric cancer patients and non-cancer donors, from Hong Kong, the US and UK.

timcoorens.bsky.social•7 days ago

We find that gastric glands are clonal units arising from a single stem cell. In non-cancer donors, the mutation rate is 28 SNVs and 2 indels per year. This is mostly true in cancer patients, but some patients have many "hypermutant" glands, with far more mutations than expected.

timcoorens.bsky.social•7 days ago

These hypermutant glands are almost exclusively in the antrum of the stomach, chronically inflamed and most importantly, metaplastic. Intestinal metaplasia is a well-known precursor to gastric cancer, but these aren't monoclonal expansions.

timcoorens.bsky.social•7 days ago

The mutational signatures are mostly SBS1, SBS5 and SBS18, like other epithelial tissues. Metaplastic glands have much more SBS1 and SBS18 (ROS), and indels linked to polymerase slippage. These are also dominant in intestinal glands, so may suggest a “rewiring” of the mutation rate.

timcoorens.bsky.social•7 days ago

While SBS17 is very common in gastric cancer, we only find it very rarely in normal glands, and only in very low proportions. So while stomach cells can get exposed to SBS17, high levels of SBS17 seem to be exclusive to overt cancer.

timcoorens.bsky.social•7 days ago

The most surprising finding, however, comes from the CNVs in the stomach. We find extraordinarily high rates of somatic whole-chromosome gains/trisomies in the stomach, mostly of chrs 20 and 13, highly concentrated in a few patients.

metamorpheus.bsky.social•7 days ago

Do you mean bagpipes?

dagams.bsky.social•7 days ago

Great to see this published now, congratulations!

vseplyarskiy.bsky.social•7 days ago

Congrats!

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