PMID- 2841597
OWN - NLM
STAT- MEDLINE
DCOM- 19880920
LR  - 20220711
IS  - 0028-4793 (Print)
IS  - 0028-4793 (Linking)
VI  - 319
IP  - 9
DP  - 1988 Sep 1
TI  - Genetic alterations during colorectal-tumor development.
PG  - 525-32
AB  - Because most colorectal carcinomas appear to arise from adenomas, studies of 
      different stages of colorectal neoplasia may shed light on the genetic 
      alterations involved in tumor progression. We looked for four genetic alterations 
      (ras-gene mutations and allelic deletions of chromosomes 5, 17, and 18) in 172 
      colorectal-tumor specimens representing various stages of neoplastic development. 
      The specimens consisted of 40 predominantly early-stage adenomas from 7 patients 
      with familial adenomatous polyposis, 40 adenomas (19 without associated foci of 
      carcinoma and 21 with such foci) from 33 patients without familial polyposis, and 
      92 carcinomas resected from 89 patients. We found that ras-gene mutations 
      occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of 
      carcinomas. However, ras mutations were found in only 9 percent of adenomas under 
      1 cm in size. Sequences on chromosome 5 that are linked to the gene for familial 
      adenomatous polyposis were not lost in adenomas from the patients with polyposis 
      but were lost in 29 to 35 percent of adenomas and carcinomas, respectively, from 
      other patients. A specific region of chromosome 18 was deleted frequently in 
      carcinomas (73 percent) and in advanced adenomas (47 percent) but only 
      occasionally in earlier-stage adenomas (11 to 13 percent). Chromosome 17p 
      sequences were usually lost only in carcinomas (75 percent). The four molecular 
      alterations accumulated in a fashion that paralleled the clinical progression of 
      tumors. These results are consistent with a model of colorectal tumorigenesis in 
      which the steps required for the development of cancer often involve the 
      mutational activation of an oncogene coupled with the loss of several genes that 
      normally suppress tumorigenesis.
FAU - Vogelstein, B
AU  - Vogelstein B
AD  - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 
      MD.
FAU - Fearon, E R
AU  - Fearon ER
FAU - Hamilton, S R
AU  - Hamilton SR
FAU - Kern, S E
AU  - Kern SE
FAU - Preisinger, A C
AU  - Preisinger AC
FAU - Leppert, M
AU  - Leppert M
FAU - Nakamura, Y
AU  - Nakamura Y
FAU - White, R
AU  - White R
FAU - Smits, A M
AU  - Smits AM
FAU - Bos, J L
AU  - Bos JL
LA  - eng
GR  - CA35494/CA/NCI NIH HHS/United States
GR  - GM07184/GM/NIGMS NIH HHS/United States
GR  - GM07309/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
SB  - IM
MH  - Adenoma/genetics
MH  - Adenomatous Polyposis Coli/genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Carcinoma/genetics
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 17
MH  - Chromosomes, Human, Pair 18
MH  - Chromosomes, Human, Pair 5
MH  - Colonic Neoplasms/*genetics
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
MH  - Female
MH  - Genes, ras
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Rectal Neoplasms/*genetics
EDAT- 1988/09/01 00:00
MHDA- 1988/09/01 00:01
CRDT- 1988/09/01 00:00
PHST- 1988/09/01 00:00 [pubmed]
PHST- 1988/09/01 00:01 [medline]
PHST- 1988/09/01 00:00 [entrez]
AID - 10.1056/NEJM198809013190901 [doi]
PST - ppublish
SO  - N Engl J Med. 1988 Sep 1;319(9):525-32. doi: 10.1056/NEJM198809013190901.