Carcinogenesis, Vol 19, 2145-2149, Copyright © 1998 by Oxford University Press
YH Shiao, D Palli, GS Buzard, NE Caporaso, A Amorosi, C Saieva, JF Fraumeni Jr, LM Anderson and JM Rice
Examination of p53 mutation spectra may provide clues to molecular
mechanisms involved in different histologic types of gastric cancer. A
total of 105 gastric cancer cases classified according to the Lauren's
system were selected from a high-risk area around Florence, Italy. Exons
5-8 of the p53 gene were examined for mutations by the polymerase chain
reaction-single strand conformation polymorphism technique and DNA
sequencing, using DNA from formalin-fixed paraffin-embedded tissues.
Mutation frequency was similar in intestinal-type (12/28) and unclassified
tumors (9/18), but was significantly lower in diffuse cancers (12/57, P
< 0.05). A similar frequency of p53 mutations was observed among tumor
stages in both intestinal-type and unclassified cancers, but in diffuse
tumors mutations tended to be associated with invasion beyond the
muscularis propria. When base changes were considered, G:C-->A:T
transitions at CpG sites were the most common mutations for all the three
tumor types with 6 of 11 (55%) in intestinal type, 8 of 12 (67%) in diffuse
type, and 5 of 8 (63 %) in unclassified tumors. Frequent p53 mutations in
both intestinal-type and unclassified tumors support the hypothesis that
unclassified tumors represent variants of the intestinal type and suggest
that unclassified tumors, like the intestinal type, may also associate with
environmental exposures. The predominance of G:C-->A:T transitions at
CpG sites, which are associated with methyltransferase-induced DNA
methylation at carbon 5 of cytosine, in all three tumor types suggests that
the status of DNA methylation may be the major determinant for p53
mutations and may be also equally important in gastric carcinogenesis
regardless of histology.
ARTICLES
Implications of p53 mutation spectrum for cancer etiology in gastric cancers of various histologic types from a high-risk area of central Italy
Laboratory of Comparative Carcinogenesis, NCI-FCRDC, Frederick, MD 21702, USA. shiao@mail.ncifcrf.gov
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Vecchione, H. Ishii, Y.-H. Shiao, F. Trapasso, M. Rugge, J. F. Tamburrino, Y. Murakumo, H. Alder, C. M. Croce, and R. Baffa Fez1/Lzts1 Alterations in Gastric Carcinoma Clin. Cancer Res., June 1, 2001; 7(6): 1546 - 1552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. E. Magnusson, H. Enroth, I. Eriksson, M. Held, O. Nyrén, L. Engstrand, L.-E. Hansson, and U. B. Gyllensten Gastric Cancer and Human Leukocyte Antigen: Distinct DQ and DR Alleles Are Associated with Development of Gastric Cancer and Infection by Helicobacter pylori Cancer Res., March 1, 2001; 61(6): 2684 - 2689. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y.-H. Shiao, D. Palli, N. E. Caporaso, W. G. Alvord, A. Amorosi, G. Nesi, C. Saieva, G. Masala, J. F. Fraumeni Jr., and J. M. Rice Genetic and Immunohistochemical Analyses of p53 Independently Predict Regional Metastasis of Gastric Cancers Cancer Epidemiol. Biomarkers Prev., June 1, 2000; 9(6): 631 - 633. [Abstract] [Full Text]
|
|
|
|
 |
|
 I TINHOFER, H WYKYPIEL, I MARSCHITZ, T HENN, R GREIL;, M W BENNETT, J O'CONNELL, D ROCHE, C BRADY, J KELLY, et al. Gastric cancer cell lines lack Fas ligand (FasL) expression but kill T cells via a FasL independent pathway • Reply Gut, May 1, 2000; 46(5): 738 - 740. [Full Text] [PDF]
|
|
|
|
|
|
R. Baffa, R. Santoro, F. Bullrich, B. Mandes, H. Ishii, and C. M. Croce Definition and Refinement of Chromosome 8p Regions of Loss of Heterozygosity in Gastric Cancer Clin. Cancer Res., April 1, 2000; 6(4): 1372 - 1377. [Abstract] [Full Text]
|
|