Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer.
OBJECTIVE
TP53 gene is frequently mutated in gastric cancer (GC), but the relationship with clinicopathological features and prognosis is conflicting. Here, we screened TP53 mutation spectrum of 214 GC patients in relation to their clinicopathological features and prognosis.


RESULTS
TP53 nonsilent mutations were detected in 80 cases (37.4%), being frequently occurred as C:G to T:A single nucleotide transitions at 5'-CpG-3' sites. TP53 mutations occurred more frequently in differentiated histologic type than in undifferentiated type in the early stage (48.6% vs. 7%, P=0.0006), while the mutations correlated with venous invasion among advanced stage (47.7% vs. 20.7%, P=0.04). Subset of GC with TP53 hot spot mutations (R175, G245, R248, R273, R282) presented significantly worse overall survival and recurrence free survival compared to others (both P=0.001).


METHODS
Matched biopsies from GC and adjacent tissues from 214 patients were used for the experiment. All coding regions of TP53 gene (exon2 to exon11) were examined using Sanger sequencing.


CONCLUSIONS
Our data suggest that GC with TP53 mutations seems to develop as differentiated histologic type and show aggressive biological behavior such as venous invasion. Moreover, our data emphasizes the importance of discriminating TP53 hot spot mutations (R175, G245, R248, R273, R282) to predict worse overall survival and recurrence free survival of GC patients.
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Tomomitsu
T
Tahara
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Tomoyuki
T
Shibata
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Yasuyuki
Y
Okamoto
Laboratory of Molecular Medicine, Hokkaido University Graduate School of Veterinary Medicine, Sapporo, Japan.
Jumpei
J
Yamazaki
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Tomohiko
T
Kawamura
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Noriyuki
N
Horiguchi
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Masaaki
M
Okubo
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Naoko
N
Nakano
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Takamitsu
T
Ishizuka
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Mitsuo
M
Nagasaka
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Yoshihito
Y
Nakagawa
Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan.
Naoki
N
Ohmiya
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002454:Cell Differentiation; D018899:CpG Islands; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
TP53 mutation; gastric cancer; hotspot mutations; spectrum; survival