Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer

Tomomitsu Tahara; Tomoyuki Shibata; Yasuyuki Okamoto; Jumpei Yamazaki; Tomohiko Kawamura; Noriyuki Horiguchi; Masaaki Okubo; Naoko Nakano; Takamitsu Ishizuka; Mitsuo Nagasaka; Yoshihito Nakagawa; Naoki Ohmiya

doi:10.18632/oncotarget.9770

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Research Papers:

Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer

Tomomitsu Tahara _, Tomoyuki Shibata, Yasuyuki Okamoto, Jumpei Yamazaki, Tomohiko Kawamura, Noriyuki Horiguchi, Masaaki Okubo, Naoko Nakano, Takamitsu Ishizuka, Mitsuo Nagasaka, Yoshihito Nakagawa and Naoki Ohmiya

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Oncotarget. 2016; 7:42252-42260. https://doi.org/10.18632/oncotarget.9770

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Abstract

Tomomitsu Tahara1, Tomoyuki Shibata1, Yasuyuki Okamoto2, Jumpei Yamazaki3, Tomohiko Kawamura1, Noriyuki Horiguchi1, Masaaki Okubo1, Naoko Nakano1, Takamitsu Ishizuka1, Mitsuo Nagasaka1, Yoshihito Nakagawa1, Naoki Ohmiya1

1Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan

2Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

3Laboratory of Molecular Medicine, Hokkaido University Graduate School of Veterinary Medicine, Sapporo, Japan

Correspondence to:

Tomomitsu Tahara, e-mail: [email protected]

Keywords: TP53 mutation, gastric cancer, spectrum, survival, hotspot mutations

Received: October 24, 2015 Accepted: April 18, 2016 Published: June 01, 2016

ABSTRACT

Background and aim: 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.

Conclusion: 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.

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Research Papers:

Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer

Abstract