Non-CpG sites preference in G:C > A:T transition of TP53 in gastric cancer of Eastern Europe (Poland, Romania and Hungary) compared to East Asian countries (China and Japan)

Hiroko Natsume; Kinga Szczepaniak; Hidetaka Yamada; Yuji Iwashita; Marta Gędek; Jelena Šuto; Keiko Ishino; Rika Kasajima; Tomonari Matsuda; Felix Manirakiza; Augustin Nzitakera; Yijia Wu; Nong Xiao; Qiong He; Wenwen Guo; Zhenming Cai; Tsutomu Ohta; Tıberiu Szekely; Zoltan Kadar; Akiko Sekiyama; Takashi Oshima; Takaki Yoshikawa; Akira Tsuburaya; Nobuhito Kurono; Yaping Wang; Yohei Miyagi; Simona Gurzu; Haruhiko Sugimura

doi:10.1186/s41021-022-00257-y

Non-CpG sites preference in G:C > A:T transition of TP53 in gastric cancer of Eastern Europe (Poland, Romania and Hungary) compared to East Asian countries (China and Japan)

Genes Environ. 2023 Jan 4;45(1):1. doi: 10.1186/s41021-022-00257-y.

Authors

Hiroko Natsume^#¹, Kinga Szczepaniak^#^{1

2}, Hidetaka Yamada^#³, Yuji Iwashita¹, Marta Gędek^{1

4}, Jelena Šuto^{1

5}, Keiko Ishino¹, Rika Kasajima^{6

7}, Tomonari Matsuda⁸, Felix Manirakiza¹, Augustin Nzitakera¹, Yijia Wu⁹, Nong Xiao¹⁰, Qiong He¹¹, Wenwen Guo^{10

11}, Zhenming Cai^{10

12}, Tsutomu Ohta^{1

13}, Tıberiu Szekely^{14

15}, Zoltan Kadar¹⁵, Akiko Sekiyama¹⁶, Takashi Oshima¹⁷, Takaki Yoshikawa¹⁸, Akira Tsuburaya¹⁹, Nobuhito Kurono²⁰, Yaping Wang²¹, Yohei Miyagi²², Simona Gurzu²³, Haruhiko Sugimura^{24

25}

Affiliations

¹ Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higasi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
² Medical University of Warsaw, 1B Banacha Street, Warsaw, Poland.
³ Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higasi-ku, Hamamatsu, Shizuoka, 431-3192, Japan. h-yamada@hama-med.ac.jp.
⁴ Medical University of Lublin, ul. Radziwiłłowska 11, wew, 5647, Lublin, Poland.
⁵ Department of Oncology, Clinical Hospital Centre Split, Split, Croatia.
⁶ The Center for Cancer Genome Medicine, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.
⁷ Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
⁸ Research Center for Environmental Quality Management, Kyoto University, 1-2 Yumihama, Otsu, Shiga, 520-0811, Japan.
⁹ Lujiang People Hospital, 32 Wenmingzhong Road, Lujiang, Hefei, 231501, China.
¹⁰ Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, 210093, China.
¹¹ Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210003, China.
¹² Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases, Nanjing Medical University, Nanjing, 211166, China.
¹³ Department of Physical Therapy, Faculty of Health and Medical Sciences, Tokoha University, 1230 Miyakoda-cho, Kita-ku, Hamamatsu, Shizuoka, 431-2102, Japan.
¹⁴ Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Ghe Marinescu 38 Street, 540139, Targu Mures, Romania.
¹⁵ Department of Oncology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Ghe Marinescu 38 Street, 540139, Targu Mures, Romania.
¹⁶ Department of Clinical Laboratory, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.
¹⁷ Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.
¹⁸ Department of Gastric Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
¹⁹ Department of Surgery, Ozawa Hospital, 1-1-17, Honcho, Odawara, Kanagawa, 250-0012, Japan.
²⁰ Department of Chemistry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
²¹ Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, 210093, China. wangyap@nju.edu.cn.
²² Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan. miyagi@gancen.asahi.yokohama.jp.
²³ Department of Pathology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Ghe Marinescu 38 Street, 540139, Targu Mures, Romania. simonagurzu@yahoo.com.
²⁴ Department of Tumor Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higasi-ku, Hamamatsu, Shizuoka, 431-3192, Japan. hsugimur@hama-med.ac.jp.
²⁵ Sasaki Foundation Sasaki Institute, 2-2, KandaSurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan. hsugimur@hama-med.ac.jp.

^# Contributed equally.

Abstract

Aim: Mutation spectrum of TP53 in gastric cancer (GC) has been investigated world-widely, but a comparison of mutation spectrum among GCs from various regions in the world are still sparsely documented. In order to identify the difference of TP53 mutation spectrum in GCs in Eastern Europe and in East Asia, we sequenced TP53 in GCs from Eastern Europe, Lujiang (China), and Yokohama, Kanagawa (Japan) and identified the feature of TP53 mutations of GC in these regions.

Subjects and method: In total, 689 tissue samples of GC were analyzed: 288 samples from East European populations (25 from Hungary, 71 from Poland and 192 from Romania), 268 from Yokohama, Kanagawa, Japan and 133 from Lujiang, Anhui province, China. DNA was extracted from FFPE tissue of Chinese, East European cases; and from frozen tissue of Japanese GCs. PCR products were direct-sequenced by Sanger method, and in ambiguous cases, PCR product was cloned and up to 8 clones were sequenced. We used No. NC_000017.11(hg38) as the reference sequence of TP53. Mutation patterns were categorized into nine groups: six base substitutions, insertion, deletion and deletion-insertion. Within G:C > A:T mutations the mutations in CpG and non-CpG sites were divided. The Cancer Genome Atlas data (TCGA, ver.R20, July, 2019) having somatic mutation list of GCs from Whites, Asians, and other ethnicities were used as a reference for our data.

Results: The most frequent base substitutions were G:C > A:T transition in all the areas investigated. The G:C > A:T transition in non-CpG sites were prominent in East European GCs, compared with Asian ones. Mutation pattern from TCGA data revealed the same trend between GCs from White (TCGA category) vs Asian countries. Chinese and Japanese GCs showed higher ratio of G:C > A:T transition in CpG sites and A:T > G:C mutation was more prevalent in Asian countries.

Conclusion: The divergence in mutation spectrum of GC in different areas in the world may reflect various pathogeneses and etiologies of GC, region to region. Diversified mutation spectrum in GC in Eastern Europe may suggest GC in Europe has different carcinogenic pathway of those from Asia.

Keywords: Adductomics; Gastric cancer; Gene-environmental interaction; Geographic; Molecular epidemiology; Mutation signature; Mutation spectrum; Pathology; TP53.

Abstract

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