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The 1988 study of 172 bowel tumours that showed cancer is not one mutation but a sequence of them, accumulating as a polyp grows into a cancer. It is the origin of the idea that cancer develops step by step.
Vogelstein, Fearon, Hamilton, Kern, Preisinger, Leppert, Nakamura, White, Smits and Bos looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17 and 18) in 172 colorectal-tumour specimens representing different stages of neoplastic development: 40 predominantly early-stage adenomas from seven patients with familial adenomatous polyposis, 40 adenomas from 33 patients without polyposis (19 without and 21 with associated foci of carcinoma), and 92 carcinomas resected from 89 patients.
The four alterations accumulated in a way that paralleled the clinical progression of the tumours, and the authors concluded that the steps to cancer often involve mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumourigenesis. Fearon and Vogelstein set the model out in full two years later in Cell (the corpus holds that record as paper-fearon-cell).
Every screening programme rests on this paper: if cancer arrives through a polyp that takes years to progress, then finding and removing polyps prevents cancer rather than merely catching it early.
The clinical proof of Vogelstein's sequence: interrupting the adenoma-carcinoma pathway with a snare prevents the cancer, which is why colonoscopy is the only screening test that both detects and prevents.
The paper that put HER2 on the colorectal map (HERACLES, MOUNTAINEER and DESTINY-CRC follow from it) and that showed the hypermutated group, later the immunotherapy-responsive group, is defined by two distinct mechanisms.
One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Shares Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths (National Polyp Study), Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Prevention we already have is not deployed, The hardest cancers are found late and the tag colorectal-evidence.
Shares Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths (National Polyp Study), Comprehensive molecular characterization of human colon and rectal cancer, Prevention we already have is not deployed, Colon cancer (adenocarcinoma of the colon) and the tag colorectal-evidence.
Shares Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths (National Polyp Study), Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), The hardest cancers are found late, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Prevention we already have is not deployed, The hardest cancers are found late, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Kenneth W. Kinzler, Bert Vogelstein, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares APC, Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Prevention we already have is not deployed, The hardest cancers are found late and the tag colorectal-evidence.
Shares Kenneth W. Kinzler, Bert Vogelstein, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Prevention we already have is not deployed, The hardest cancers are found late, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.