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

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Abstract

// Tomomitsu Tahara 1 , Tomoyuki Shibata 1 , Yasuyuki Okamoto 2 , Jumpei Yamazaki 3 , Tomohiko Kawamura 1 , Noriyuki Horiguchi 1 , Masaaki Okubo 1 , Naoko Nakano 1 , Takamitsu Ishizuka 1 , Mitsuo Nagasaka 1 , Yoshihito Nakagawa 1 , Naoki Ohmiya 1 1 Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan 2 Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 3 Laboratory of Molecular Medicine, Hokkaido University Graduate School of Veterinary Medicine, Sapporo, Japan Correspondence to: Tomomitsu Tahara, e-mail: tomomiccyu@yahoo.co.jp 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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