[Point mutation of TP53 suppressor gene in pre-neoplastic and neoplastic lesions of the stomach].
BACKGROUND
In the current model for the development of gastric cancer, regions of multifocal atrophic gastritis give rise to intestinal metaplasia, dysplasia and finally, adenocarcinoma.


OBJECTIVE
To study the frequency and characteristics of TP53 gene mutations in preneoplastic and neoplastic lesions of the stomach.


METHODS
DNA sequencing of the TP53 gene was performed in 46 patients with gastric carcinoma. Normal mucosa, intestinal metaplasia and invasive adenocarcinoma tissues were obtained by scraping 6-micron histological sections from formalin-fixed and paraffin-embedded tissue.


RESULTS
DNA sequencing of exons 5-9 of the TP53 gene demonstrated a mutation in 31% of patients. These findings were seen both in tumoral tissue (13 cases) and in intestinal metaplasia (2 cases). Most mutations were found in exons 5 and 8, and the majority of them were transitions (10 out of 19 mutations).


CONCLUSIONS
Patients with gastric cancer showed a frequency of TP53 mutations similar to that previously communicated in populations with low gastric cancer risk. Moreover, there was a predominance of transitions, genetic alterations that are identified with carcinogenesis associated with N-nitrosamine compounds. Finally, mutations of TP53 gene were detected in areas of intestinal metaplasia.
Araya
Juan Carlos
JC
Departamento de Anatomía Patológica, Facultad de Medicina, Universidad de La Frontera, Casilla 54-D, Temuco, Chile. jcaraya@ufro.cl
Roa
Juan Carlos
JC
Villaseca
Miguel Angel
MA
Roa
Iván
I
Guzmán
Pablo
P
Alvarado
César
C
Melo
Angélica
A
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology