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 Omiya

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)42252-42260
Number of pages9
JournalOncotarget
Volume7
Issue number27
DOIs
Publication statusPublished - 05-07-2016

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p53 Genes
Stomach Neoplasms
Mutation
Survival
Recurrence
Nucleotides
Biopsy

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Tahara, Tomomitsu ; Shibata, Tomoyuki ; Okamoto, Yasuyuki ; Yamazaki, Jumpei ; Kawamura, Tomohiko ; Horiguchi, Noriyuki ; Okubo, Masaaki ; Nakano, Naoko ; Ishizuka, Takamitsu ; Nagasaka, Mitsuo ; Nakagawa, Yoshihito ; Omiya, Naoki. / Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer. In: Oncotarget. 2016 ; Vol. 7, No. 27. pp. 42252-42260.
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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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Tahara, T, Shibata, T, Okamoto, Y, Yamazaki, J, Kawamura, T, Horiguchi, N, Okubo, M, Nakano, N, Ishizuka, T, Nagasaka, M, Nakagawa, Y & Omiya, N 2016, 'Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer', Oncotarget, vol. 7, no. 27, pp. 42252-42260. https://doi.org/10.18632/oncotarget.9770

Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer. / Tahara, Tomomitsu; Shibata, Tomoyuki; Okamoto, Yasuyuki; Yamazaki, Jumpei; Kawamura, Tomohiko; Horiguchi, Noriyuki; Okubo, Masaaki; Nakano, Naoko; Ishizuka, Takamitsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Omiya, Naoki.

In: Oncotarget, Vol. 7, No. 27, 05.07.2016, p. 42252-42260.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mutation spectrum of TP53 gene predicts clinicopathological features and survival of gastric cancer

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Okamoto, Yasuyuki

AU - Yamazaki, Jumpei

AU - Kawamura, Tomohiko

AU - Horiguchi, Noriyuki

AU - Okubo, Masaaki

AU - Nakano, Naoko

AU - Ishizuka, Takamitsu

AU - Nagasaka, Mitsuo

AU - Nakagawa, Yoshihito

AU - Omiya, Naoki

PY - 2016/7/5

Y1 - 2016/7/5

N2 - 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.

AB - 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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