Most of what we thought we knew about how colon cancer starts is wrong for 66% of patients.
April 16, 2026
Original Paper
Single-crypt evolutionary trajectories of human sporadic and hereditary colorectal precancers
bioRxiv · 10.64898/2026.04.13.718204
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The Takeaway
For decades, the "APC mutation" was considered the mandatory first step for colon cancer—the spark that starts the fire. But this new study looked at pre-cancerous polyps and found that a massive 66% of them didn't have that mutation at all. This means there are shadow pathways to cancer that we’ve been completely ignoring because they don't follow the textbook rules. It’s a major "holy shit" moment for oncology because it means our current screening methods might be looking for the wrong first signs. To save lives, we need to rewrite the map of how one of the world's most common cancers actually begins.
From the abstract
Our understanding of the earliest genomic processes and evolutionary trajectories that distinguish sporadic from hereditary human cancers remains limited, impeding early diagnosis and risk stratification. Here, we performed whole-genome sequencing of 319 single crypts dissected from normal colorectal mucosa, premalignant polyps and malignant colorectal cancers (CRCs) from five sporadic patients and three familial adenomatous polyposis (FAP) patients. We found 66% of premalignant crypts from spor