# Adenoma-carcinoma sequence

Source: https://onco.cc/terms/adenoma-carcinoma-sequence/  
OnCo record `adenoma-carcinoma-sequence` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The adenoma-carcinoma sequence is the step-by-step route by which a normal bowel lining becomes a polyp and the polyp becomes a cancer, as genetic faults pile up over years. It is why removing polyps prevents cancer, and it was the first human cancer to be mapped this way.

## Summary

The sequence was mapped in 172 colorectal specimens representing every stage from small adenoma to carcinoma. RAS mutations were present in 58 percent of adenomas larger than 1 cm but in only 9 percent of adenomas under 1 cm; the chromosome 5 region carrying the polyposis gene was lost in 29 to 35 percent of adenomas and carcinomas from patients without polyposis; a region of chromosome 18 was deleted in 73 percent of carcinomas, 47 percent of advanced adenomas and 11 to 13 percent of early adenomas; and chromosome 17p was usually lost only in carcinomas (75 percent). The four alterations accumulated in step with clinical progression, which is the observation the model rests on (Vogelstein 1988). The 1990 synthesis generalised it: cancer arises from the mutational activation of oncogenes coupled with the inactivation of several tumour suppressor genes, at least four or five alterations are needed, and it is the accumulation rather than the order that determines the biology, so tumours with the same set of changes but acquired in different orders behave alike (Fearon and Vogelstein 1990).

What it means in practice. First, time: the years an adenoma takes to become a carcinoma are the window screening works in. Second, prevention: if the polyp is the obligate precursor, removing it should prevent the cancer, and the National Polyp Study showed exactly that, with 76 to 90 percent fewer cancers than expected in 1,418 patients whose adenomas were removed and 53 percent lower colorectal cancer mortality at a median of 15.8 years (Winawer 1993; Zauber 2012). Third, limits: this is not the only route. About 30 percent of colorectal carcinomas arise through the serrated pathway instead, from flatter lesions with promoter methylation and BRAF or KRAS mutation, and those are the lesions screening misses most often (Bettington 2013). The sequence also underlies familial adenomatous polyposis, where the gatekeeper gene APC is lost in the germline and the field of adenomas is enormous.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: adenoma to carcinoma sequence; Vogelstein model; chromosomal instability pathway; conventional pathway; APC-KRAS-TP53 sequence
- Tags: gi; colorectal

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Colorectal_cancer
- Vogelstein, N Engl J Med 1988: genetic alterations during colorectal tumour development (172 specimens): https://doi.org/10.1056/nejm198809013190901
- Fearon and Vogelstein, Cell 1990: a genetic model for colorectal tumorigenesis: https://doi.org/10.1016/0092-8674(90)90186-i
- Winawer, N Engl J Med 1993: prevention of colorectal cancer by colonoscopic polypectomy (National Polyp Study, 1,418 patients): https://doi.org/10.1056/nejm199312303292701
- Zauber, N Engl J Med 2012: colonoscopic polypectomy and long-term prevention of colorectal cancer deaths (National Polyp Study, 2,602 patients): https://doi.org/10.1056/nejmoa1100370
- Bettington, Histopathology 2013: the serrated pathway to colorectal carcinoma, current concepts and challenges: https://doi.org/10.1111/his.12055

## Connected records

- cancers: [Adenoma-like adenocarcinoma of the colon and rectum](https://onco.cc/cancers/colorectal-adenoma-like-adenocarcinoma/), [Colon cancer (adenocarcinoma of the colon)](https://onco.cc/cancers/colon-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Familial adenomatous polyposis-associated colorectal cancer](https://onco.cc/cancers/fap-associated-colorectal-cancer/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- technologies: [Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)](https://onco.cc/technologies/colorectal-screening/)
- targets: [KRAS](https://onco.cc/targets/kras/), [TP53](https://onco.cc/targets/tp53/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [Colibactin](https://onco.cc/terms/colibactin/), [Colonoscopy](https://onco.cc/terms/colonoscopy/), [Consensus molecular subtypes (CMS1-4)](https://onco.cc/terms/cms-subtypes/), [Polyp types in the bowel](https://onco.cc/terms/colorectal-polyp-types/), [R-spondin fusion](https://onco.cc/terms/rspo-fusion/), [Serrated pathway](https://onco.cc/terms/serrated-pathway/), [Surveillance intervals after polypectomy](https://onco.cc/terms/colonoscopy-surveillance-intervals/)

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