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47 results on '"Inoue, Yoshikage"'

1. Frequent ZNF217 mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma

Author

Briest, Franziska, Noerenberg, Daniel, Hennch, Cornelius, Yoshida, Kenichi, Hablesreiter, Raphael, Nimo, Jose, Sasca, Daniel, Kirchner, Marieluise, Mansouri, Larry, Inoue, Yoshikage, Wiegand, Laura, Staiger, Annette M., Casadei, Beatrice, Korkolopoulou, Penelope, Weiner, January, Lopez-Guillermo, Armando, Warth, Arne, Schneider, Tamás, Nagy, Ákos, Klapper, Wolfram, Hummel, Michael, Kanellis, George, Anagnostopoulos, Ioannis, Mertins, Philipp, Bullinger, Lars, Rosenquist, Richard, Vassilakopoulos, Theodoros P., Ott, German, Ogawa, Seishi, and Damm, Frederik

Published
2023
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3. Molecular classification and diagnostics of upper urinary tract urothelial carcinoma

Author

Fujii, Yoichi, Sato, Yusuke, Suzuki, Hiromichi, Kakiuchi, Nobuyuki, Yoshizato, Tetsuichi, Lenis, Andrew T., Maekawa, Shigekatsu, Yokoyama, Akira, Takeuchi, Yasuhide, Inoue, Yoshikage, Ochi, Yotaro, Shiozawa, Yusuke, Aoki, Kosuke, Yoshida, Kenichi, Kataoka, Keisuke, Nakagawa, Masahiro M., Nannya, Yasuhito, Makishima, Hideki, Miyakawa, Jimpei, Kawai, Taketo, Morikawa, Teppei, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Nagae, Genta, Sanada, Masashi, Sugihara, Eiji, Sato, Taka-Aki, Nakagawa, Tohru, Fukayama, Masashi, Ushiku, Tetsuo, Aburatani, Hiroyuki, Miyano, Satoru, Coleman, Jonathan A., Homma, Yukio, Solit, David B., Kume, Haruki, and Ogawa, Seishi

Published
2021
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4. Frequent genetic alterations in immune checkpoint–related genes in intravascular large B-cell lymphoma

Author

Shimada, Kazuyuki, Yoshida, Kenichi, Suzuki, Yasuhiro, Iriyama, Chisako, Inoue, Yoshikage, Sanada, Masashi, Kataoka, Keisuke, Yuge, Masaaki, Takagi, Yusuke, Kusumoto, Shigeru, Masaki, Yasufumi, Ito, Takahiko, Inagaki, Yuichiro, Okamoto, Akinao, Kuwatsuka, Yachiyo, Nakatochi, Masahiro, Shimada, Satoko, Miyoshi, Hiroaki, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Miyano, Satoru, Shiozawa, Yusuke, Nannya, Yasuhito, Okabe, Asako, Kohno, Kei, Atsuta, Yoshiko, Ohshima, Koichi, Nakamura, Shigeo, Ogawa, Seishi, Tomita, Akihiro, and Kiyoi, Hitoshi

Published
2021
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5. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis

Author

Kakiuchi, Nobuyuki, Yoshida, Kenichi, Uchino, Motoi, Kihara, Takako, Akaki, Kotaro, Inoue, Yoshikage, and Kawada, Kenji

Subjects
Analysis, Genetic aspects, Forecasts and trends, Market trend/market analysis, Interleukin-17 -- Analysis, Ulcerative colitis -- Genetic aspects, Gene mutation -- Forecasts and trends, Transcription factors -- Analysis, Gene mutations -- Forecasts and trends
Abstract

Author(s): Nobuyuki Kakiuchi [sup.1] [sup.2] [sup.3] , Kenichi Yoshida [sup.1] , Motoi Uchino [sup.4] , Takako Kihara [sup.5] , Kotaro Akaki [sup.6] , Yoshikage Inoue [sup.1] [sup.2] [sup.7] , Kenji [...], Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer.sup.1-3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer. In patients with ulcerative colitis, chronic inflammation can lead to remodelling of the colorectal epithelium through positive selection of clones with mutations in genes related to IL-17 signalling, which, however, might be negatively selected during colitis-associated carcinogenesis.

Published
2020
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6. Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

Author

Inagaki-Kawata, Yukiko, Yoshida, Kenichi, Kawaguchi-Sakita, Nobuko, Kawashima, Masahiro, Nishimura, Tomomi, Senda, Noriko, Shiozawa, Yusuke, Takeuchi, Yasuhide, Inoue, Yoshikage, Sato-Otsubo, Aiko, Fujii, Yoichi, Nannya, Yasuhito, Suzuki, Eiji, Takada, Masahiro, Tanaka, Hiroko, Shiraishi, Yuichi, Chiba, Kenichi, Kataoka, Yuki, Torii, Masae, Yoshibayashi, Hiroshi, Yamagami, Kazuhiko, Okamura, Ryuji, Moriguchi, Yoshio, Kato, Hironori, Tsuyuki, Shigeru, Yamauchi, Akira, Suwa, Hirofumi, Inamoto, Takashi, Miyano, Satoru, Ogawa, Seishi, and Toi, Masakazu

Published
2020
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7. Age-related remodelling of oesophageal epithelia by mutated cancer drivers

Author

Yokoyama, Akira, Kakiuchi, Nobuyuki, Yoshizato, Tetsuichi, Nannya, Yasuhito, Suzuki, Hiromichi, Takeuchi, Yasuhide, Shiozawa, Yusuke, Sato, Yusuke, Aoki, Kosuke, Kim, Soo Ki, Fujii, Yoichi, Yoshida, Kenichi, Kataoka, Keisuke, Nakagawa, Masahiro M., Inoue, Yoshikage, Hirano, Tomonori, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Sanada, Masashi, Nishikawa, Yoshitaka, Amanuma, Yusuke, Ohashi, Shinya, Aoyama, Ikuo, Horimatsu, Takahiro, Miyamoto, Shin’ichi, Tsunoda, Shigeru, Sakai, Yoshiharu, Narahara, Maiko, Brown, J. B., Sato, Yoshitaka, Sawada, Genta, Mimori, Koshi, Minamiguchi, Sachiko, Haga, Hironori, Seno, Hiroshi, Miyano, Satoru, Makishima, Hideki, Muto, Manabu, and Ogawa, Seishi

Published
2019
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8. Abstract 978: Genomic characterization and risk stratification of colorectal cancer

Author

Inoue, Yoshikage, primary, Kakiuchi, Nobuyuki, additional, Yoshida, Kenichi, additional, Nanya, Yasuhito, additional, Takeuchi, Yasuhide, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Yoshizato, Tetusichi, additional, Tanaka, Hiroko, additional, Nagayama, Satoshi, additional, Obama, Kazutaka, additional, Miyano, Satoru, additional, and Ogawa, Seishi, additional

Published
2023
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9. Supplementary Figures from Integrated Molecular Characterization of the Lethal Pediatric Cancer Pancreatoblastoma

Author

Isobe, Tomoya, primary, Seki, Masafumi, primary, Yoshida, Kenichi, primary, Sekiguchi, Masahiro, primary, Shiozawa, Yusuke, primary, Shiraishi, Yuichi, primary, Kimura, Shunsuke, primary, Yoshida, Misa, primary, Inoue, Yoshikage, primary, Yokoyama, Akira, primary, Kakiuchi, Nobuyuki, primary, Suzuki, Hiromichi, primary, Kataoka, Keisuke, primary, Sato, Yusuke, primary, Kawai, Tomoko, primary, Chiba, Kenichi, primary, Tanaka, Hiroko, primary, Shimamura, Teppei, primary, Kato, Motohiro, primary, Iguchi, Akihiro, primary, Hama, Asahito, primary, Taguchi, Tomoaki, primary, Akiyama, Masaharu, primary, Fujimura, Junya, primary, Inoue, Akiko, primary, Ito, Tsuyoshi, primary, Deguchi, Takao, primary, Kiyotani, Chikako, primary, Iehara, Tomoko, primary, Hosoi, Hajime, primary, Oka, Akira, primary, Sanada, Masashi, primary, Tanaka, Yukichi, primary, Hata, Kenichiro, primary, Miyano, Satoru, primary, Ogawa, Seishi, primary, and Takita, Junko, primary

Published
2023
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10. Supplementary Tables from Integrated Molecular Characterization of the Lethal Pediatric Cancer Pancreatoblastoma

Author

Isobe, Tomoya, primary, Seki, Masafumi, primary, Yoshida, Kenichi, primary, Sekiguchi, Masahiro, primary, Shiozawa, Yusuke, primary, Shiraishi, Yuichi, primary, Kimura, Shunsuke, primary, Yoshida, Misa, primary, Inoue, Yoshikage, primary, Yokoyama, Akira, primary, Kakiuchi, Nobuyuki, primary, Suzuki, Hiromichi, primary, Kataoka, Keisuke, primary, Sato, Yusuke, primary, Kawai, Tomoko, primary, Chiba, Kenichi, primary, Tanaka, Hiroko, primary, Shimamura, Teppei, primary, Kato, Motohiro, primary, Iguchi, Akihiro, primary, Hama, Asahito, primary, Taguchi, Tomoaki, primary, Akiyama, Masaharu, primary, Fujimura, Junya, primary, Inoue, Akiko, primary, Ito, Tsuyoshi, primary, Deguchi, Takao, primary, Kiyotani, Chikako, primary, Iehara, Tomoko, primary, Hosoi, Hajime, primary, Oka, Akira, primary, Sanada, Masashi, primary, Tanaka, Yukichi, primary, Hata, Kenichiro, primary, Miyano, Satoru, primary, Ogawa, Seishi, primary, and Takita, Junko, primary

Published
2023
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11. Figure S6 from Unbiased Detection of Driver Mutations in Extramammary Paget Disease

Author

Ishida, Yoshihiro, primary, Kakiuchi, Nobuyuki, primary, Yoshida, Kenichi, primary, Inoue, Yoshikage, primary, Irie, Hiroyuki, primary, Kataoka, Tatsuki R., primary, Hirata, Masahiro, primary, Funakoshi, Takeru, primary, Matsushita, Shigeto, primary, Hata, Hiroo, primary, Uchi, Hiroshi, primary, Yamamoto, Yuki, primary, Fujisawa, Yasuhiro, primary, Fujimura, Taku, primary, Saiki, Ryunosuke, primary, Takeuchi, Kengo, primary, Shiraishi, Yuichi, primary, Chiba, Kenichi, primary, Tanaka, Hiroko, primary, Otsuka, Atsushi, primary, Miyano, Satoru, primary, Kabashima, Kenji, primary, and Ogawa, Seishi, primary

Published
2023
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12. Supplementary Data from Unbiased Detection of Driver Mutations in Extramammary Paget Disease

Author

Ishida, Yoshihiro, primary, Kakiuchi, Nobuyuki, primary, Yoshida, Kenichi, primary, Inoue, Yoshikage, primary, Irie, Hiroyuki, primary, Kataoka, Tatsuki R., primary, Hirata, Masahiro, primary, Funakoshi, Takeru, primary, Matsushita, Shigeto, primary, Hata, Hiroo, primary, Uchi, Hiroshi, primary, Yamamoto, Yuki, primary, Fujisawa, Yasuhiro, primary, Fujimura, Taku, primary, Saiki, Ryunosuke, primary, Takeuchi, Kengo, primary, Shiraishi, Yuichi, primary, Chiba, Kenichi, primary, Tanaka, Hiroko, primary, Otsuka, Atsushi, primary, Miyano, Satoru, primary, Kabashima, Kenji, primary, and Ogawa, Seishi, primary

Published
2023
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15. The landscape of genetic aberrations in myxofibrosarcoma

Author

90839721, 20515514, 60451811, 40402127, 10252462, Takeuchi, Yasuhide, Yoshida, Kenichi, Halik, Adriane, Kunitz, Annegret, Suzuki, Hiromichi, Kakiuchi, Nobuyuki, Shiozawa, Yusuke, Yokoyama, Akira, Inoue, Yoshikage, Hirano, Tomonori, Yoshizato, Tetsuichi, Aoki, Kosuke, Fujii, Yoichi, Nannya, Yasuhito, Makishima, Hideki, Pfitzner, Berit Maria, Bullinger, Lars, Hirata, Masahiro, Jinnouchi, Keita, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Miyano, Satoru, Okamoto, Takeshi, Haga, Hironori, Ogawa, Seishi, Damm, Frederik, 90839721, 20515514, 60451811, 40402127, 10252462, Takeuchi, Yasuhide, Yoshida, Kenichi, Halik, Adriane, Kunitz, Annegret, Suzuki, Hiromichi, Kakiuchi, Nobuyuki, Shiozawa, Yusuke, Yokoyama, Akira, Inoue, Yoshikage, Hirano, Tomonori, Yoshizato, Tetsuichi, Aoki, Kosuke, Fujii, Yoichi, Nannya, Yasuhito, Makishima, Hideki, Pfitzner, Berit Maria, Bullinger, Lars, Hirata, Masahiro, Jinnouchi, Keita, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Miyano, Satoru, Okamoto, Takeshi, Haga, Hironori, Ogawa, Seishi, and Damm, Frederik

Abstract

Myxofibrosarcoma (MFS) is a rare subtype of sarcoma, whose genetic basis is poorly understood. We analyzed 69 MFS cases using whole-genome (WGS), whole-exome (WES) and/or targeted-sequencing (TS). Newly sequenced genomic data were combined with additional deposited 116 MFS samples. WGS identified a high number of structural variations (SVs) per tumor most frequently affecting the TP53 and RB1 loci, 40% of tumors showed a BRCAness-associated mutation signature, and evidence of chromothripsis was found in all cases. Most frequently mutated/copy number altered genes affected known disease drivers such as TP53 (56.2%), CDKN2A/B (29.7%), RB1 (27.0%), ATRX (19.5%) and HDLBP (18.9%). Several previously unappreciated genetic aberrations including MUC17, FLG and ZNF780A were identified in more than 20% of patients. Longitudinal analysis of paired diagnosis and relapse time points revealed a 1.2-fold mutation number increase accompanied with substantial changes in clonal composition over time. Our study highlights the genetic complexity underlying sarcomagenesis of MFS.

Published
2022

16. Frequent ZNF217mutations lead to transcriptional deregulation of interferon signal transduction via altered chromatin accessibility in B cell lymphoma

Author

Briest, Franziska, Noerenberg, Daniel, Hennch, Cornelius, Yoshida, Kenichi, Hablesreiter, Raphael, Nimo, Jose, Sasca, Daniel, Kirchner, Marieluise, Mansouri, Larry, Inoue, Yoshikage, Wiegand, Laura, Staiger, Annette M., Casadei, Beatrice, Korkolopoulou, Penelope, Weiner, January, Lopez-Guillermo, Armando, Warth, Arne, Schneider, Tamás, Nagy, Ákos, Klapper, Wolfram, Hummel, Michael, Kanellis, George, Anagnostopoulos, Ioannis, Mertins, Philipp, Bullinger, Lars, Rosenquist, Richard, Vassilakopoulos, Theodoros P., Ott, German, Ogawa, Seishi, and Damm, Frederik

Abstract

Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n= 120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and aberrant differentiation. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure.

Published
2023
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17. The landscape of genetic aberrations in myxofibrosarcoma

Author

Takeuchi, Yasuhide, primary, Yoshida, Kenichi, additional, Halik, Adriane, additional, Kunitz, Annegret, additional, Suzuki, Hiromichi, additional, Kakiuchi, Nobuyuki, additional, Shiozawa, Yusuke, additional, Yokoyama, Akira, additional, Inoue, Yoshikage, additional, Hirano, Tomonori, additional, Yoshizato, Tetsuichi, additional, Aoki, Kosuke, additional, Fujii, Yoichi, additional, Nannya, Yasuhito, additional, Makishima, Hideki, additional, Pfitzner, Berit Maria, additional, Bullinger, Lars, additional, Hirata, Masahiro, additional, Jinnouchi, Keita, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Miyano, Satoru, additional, Okamoto, Takeshi, additional, Haga, Hironori, additional, Ogawa, Seishi, additional, and Damm, Frederik, additional

Published
2022
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19. Abstract 2675: Clonal expansion of skin keratinocyte

Author

Ishida, Yoshihiro, primary, Kakiuchi, Nobuyuki, additional, Fujii, Yoichi, additional, Hirano, Tomonori, additional, Inoue, Yoshikage, additional, Nishimura, Tomomi, additional, Ogasawara, Tatsuki, additional, Maeda, Hirona, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Miyano, Satoru, additional, Otsuka, Atsushi, additional, Kabashima, Kenji, additional, and Ogawa, Seishi, additional

Published
2021
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20. Abstract 2276: Genetic classification of colorectal cancer

Author

Inoue, Yoshikage, primary, Kakiuchi, Nobuyuki, additional, Yoshida, Kenichi, additional, Nanya, Yasuhito, additional, Shiozawa, Yusuke, additional, Takeuchi, Yasuhide, additional, Fujii, Yoichi, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Yoshizato, Tetsuichi, additional, Nagayama, Satoshi, additional, Sakai, Yoshiharu, additional, and Ogawa, Seishi, additional

Published
2021
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21. Molecular classification and diagnostics of upper urinary tract urothelial carcinoma

Author

90839721, 20515514, 80646373, 40883707, 60451811, 40402127, Fujii, Yoichi, Sato, Yusuke, Suzuki, Hiromichi, Kakiuchi, Nobuyuki, Yoshizato, Tetsuichi, Lenis, Andrew T., Maekawa, Shigekatsu, Yokoyama, Akira, Takeuchi, Yasuhide, Inoue, Yoshikage, Ochi, Yotaro, Shiozawa, Yusuke, Aoki, Kosuke, Yoshida, Kenichi, Kataoka, Keisuke, Nakagawa, Masahiro M., Nannya, Yasuhito, Makishima, Hideki, Miyakawa, Jimpei, Kawai, Taketo, Morikawa, Teppei, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Nagae, Genta, Sanada, Masashi, Sugihara, Eiji, Sato, Taka-Aki, Nakagawa, Tohru, Fukayama, Masashi, Ushiku, Tetsuo, Aburatani, Hiroyuki, Miyano, Satoru, Coleman, Jonathan A., Homma, Yukio, Solit, David B., Kume, Haruki, Ogawa, Seishi, 90839721, 20515514, 80646373, 40883707, 60451811, 40402127, Fujii, Yoichi, Sato, Yusuke, Suzuki, Hiromichi, Kakiuchi, Nobuyuki, Yoshizato, Tetsuichi, Lenis, Andrew T., Maekawa, Shigekatsu, Yokoyama, Akira, Takeuchi, Yasuhide, Inoue, Yoshikage, Ochi, Yotaro, Shiozawa, Yusuke, Aoki, Kosuke, Yoshida, Kenichi, Kataoka, Keisuke, Nakagawa, Masahiro M., Nannya, Yasuhito, Makishima, Hideki, Miyakawa, Jimpei, Kawai, Taketo, Morikawa, Teppei, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Nagae, Genta, Sanada, Masashi, Sugihara, Eiji, Sato, Taka-Aki, Nakagawa, Tohru, Fukayama, Masashi, Ushiku, Tetsuo, Aburatani, Hiroyuki, Miyano, Satoru, Coleman, Jonathan A., Homma, Yukio, Solit, David B., Kume, Haruki, and Ogawa, Seishi

Abstract

Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification. According to the mutational status of TP53, MDM2, RAS, and FGFR3, UTUC is classified into five subtypes having discrete profiles of gene expression, tumor location/histology, and clinical outcome, which is largely recapitulated in an independent UTUC cohort. Sequencing of urine sediment-derived DNA has a high diagnostic value for UTUC with 82.2% sensitivity and 100% specificity. These results provide a solid basis for better diagnosis and management of UTUC.

Published
2021

23. Unbiased Detection of Driver Mutations in Extramammary Paget Disease

Author

Ishida, Yoshihiro, primary, Kakiuchi, Nobuyuki, additional, Yoshida, Kenichi, additional, Inoue, Yoshikage, additional, Irie, Hiroyuki, additional, Kataoka, Tatsuki R., additional, Hirata, Masahiro, additional, Funakoshi, Takeru, additional, Matsushita, Shigeto, additional, Hata, Hiroo, additional, Uchi, Hiroshi, additional, Yamamoto, Yuki, additional, Fujisawa, Yasuhiro, additional, Fujimura, Taku, additional, Saiki, Ryunosuke, additional, Takeuchi, Kengo, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Otsuka, Atsushi, additional, Miyano, Satoru, additional, Kabashima, Kenji, additional, and Ogawa, Seishi, additional

Published
2020
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24. Abstract 5875: Analysis of clonal expansion in epithelium affected by ulcerative colitis reveals frequent mutations affecting IL-17 signaling pathway and novel cancer vulnerability

Author

Kakiuchi, Nobuyuki, primary, Yoshida, Kenichi, additional, Uchino, Motoi, additional, Kihara, Takako, additional, Kotaro, Akaki, additional, Inoue, Yoshikage, additional, Kawada, Kenji, additional, Nagayama, Satoshi, additional, Yokoyama, Akira, additional, Hirano, Tomonori, additional, Takeuchi, Yasuhide, additional, Miyoshi, Hiroyuki, additional, Sakai, Yoshiharu, additional, Haga, Hironori, additional, Hirota, Seiichi, additional, Ikeuchi, Hiroki, additional, Takeuchi, Osamu, additional, Miyano, Satoru, additional, Seno, Hiroshi, additional, and Ogawa, Seishi, additional

Published
2020
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25. Abstract 225: Frequent abnormalities in TP53 and increased genetic instability in myxofibrosarcoma

Author

Takeuchi, Yasuhide, primary, Kunitz, Annegret, additional, Halik, Adriane, additional, Suzuki, Hiromichi, additional, Yoshida, Kenichi, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Kakiuchi, Nobuyuki, additional, Shiozawa, Yusuke, additional, Yokoyama, Akira, additional, Inoue, Yoshikage, additional, Yoshizato, Tetsuichi, additional, Aoki, Kosuke, additional, Fujii, Yoichi, additional, Nannya, Yasuhito, additional, Makishima, Hideki, additional, Miyano, Satoru, additional, Haga, Hironori, additional, Damm, Frederik, additional, and Ogawa, Seishi, additional

Published
2020
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26. Abstract 5877: Genetic analysis of metachronous pancreatic cancers

Author

Tomonori, Hirano, primary, Kakiuchi, Nobuyuki, additional, Takeuchi, Yasuhide, additional, Inoue, Yoshikage, additional, Nishimura, Tomomi, additional, Fujii, Yoichi, additional, Yokoyama, Akira, additional, Makishima, Hideki, additional, Masui, Toshihiko, additional, Uemoto, Shinji, additional, Minamiguchi, Sachiko, additional, Haga, Hironori, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Shiraishi, Yuichi, additional, Miyano, Satoru, additional, Uza, Norimitsu, additional, Kodama, Yuzo, additional, Seno, Hiroshi, additional, and Ogawa, Seishi, additional

Published
2020
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27. Abstract 3547: Frequent genomic alterations to evade the immune system in colorectal cancer with POLE gene mutation

Author

Inoue, Yoshikage, primary, Kakiuchi, Nobuyuki, additional, Yoshida, Kenichi, additional, Takeuchi, Yasuhide, additional, Shiozawa, Yusuke, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Yoshizato, Tetsuichi, additional, Tanaka, Hiroko, additional, Okada, Ai, additional, Nagayama, Satoshi, additional, Miyano, Satoru, additional, Sakai, Yoshiharu, additional, and Ogawa, Seishi, additional

Published
2020
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28. Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

Author

80766676, 80646373, 60451811, 00612897, 50452363, 10207516, Inagaki-Kawata, Yukiko, Yoshida, Kenichi, Kawaguchi-Sakita, Nobuko, Kawashima, Masahiro, Nishimura, Tomomi, Senda, Noriko, Shiozawa, Yusuke, Takeuchi, Yasuhide, Inoue, Yoshikage, Sato-Otsubo, Aiko, Fujii, Yoichi, Nannya, Yasuhito, Suzuki, Eiji, Takada, Masahiro, Tanaka, Hiroko, Shiraishi, Yuichi, Chiba, Kenichi, Kataoka, Yuki, Torii, Masae, Yoshibayashi, Hiroshi, Yamagami, Kazuhiko, Okamura, Ryuji, Moriguchi, Yoshio, Kato, Hironori, Tsuyuki, Shigeru, Yamauchi, Akira, Suwa, Hirofumi, Inamoto, Takashi, Miyano, Satoru, Ogawa, Seishi, Toi, Masakazu, 80766676, 80646373, 60451811, 00612897, 50452363, 10207516, Inagaki-Kawata, Yukiko, Yoshida, Kenichi, Kawaguchi-Sakita, Nobuko, Kawashima, Masahiro, Nishimura, Tomomi, Senda, Noriko, Shiozawa, Yusuke, Takeuchi, Yasuhide, Inoue, Yoshikage, Sato-Otsubo, Aiko, Fujii, Yoichi, Nannya, Yasuhito, Suzuki, Eiji, Takada, Masahiro, Tanaka, Hiroko, Shiraishi, Yuichi, Chiba, Kenichi, Kataoka, Yuki, Torii, Masae, Yoshibayashi, Hiroshi, Yamagami, Kazuhiko, Okamura, Ryuji, Moriguchi, Yoshio, Kato, Hironori, Tsuyuki, Shigeru, Yamauchi, Akira, Suwa, Hirofumi, Inamoto, Takashi, Miyano, Satoru, Ogawa, Seishi, and Toi, Masakazu

Abstract

The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.

Published
2020

29. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis

Author

90839721, 90322651, 20515514, 00789638, 40511829, 80646373, 40883707, 20772403, 70335454, 40402127, 10252462, 10379092, 90335266, Kakiuchi, Nobuyuki, Yoshida, Kenichi, Uchino, Motoi, Kihara, Takako, Akaki, Kotaro, Inoue, Yoshikage, Kawada, Kenji, Nagayama, Satoshi, Yokoyama, Akira, Yamamoto, Shuji, Matsuura, Minoru, Horimatsu, Takahiro, Hirano, Tomonori, Goto, Norihiro, Takeuchi, Yasuhide, Ochi, Yotaro, Shiozawa, Yusuke, Kogure, Yasunori, Watatani, Yosaku, Fujii, Yoichi, Kim, Soo Ki, Kon, Ayana, Kataoka, Keisuke, Yoshizato, Tetsuichi, Nakagawa, Masahiro M., Yoda, Akinori, Nanya, Yasuhito, Makishima, Hideki, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Sanada, Masashi, Sugihara, Eiji, Sato, Taka-aki, Maruyama, Takashi, Miyoshi, Hiroyuki, Taketo, Makoto Mark, Oishi, Jun, Inagaki, Ryosaku, Ueda, Yutaka, Okamoto, Shinya, Okajima, Hideaki, Sakai, Yoshiharu, Sakurai, Takaki, Haga, Hironori, Hirota, Seiichi, Ikeuchi, Hiroki, Nakase, Hiroshi, Marusawa, Hiroyuki, Chiba, Tsutomu, Takeuchi, Osamu, Miyano, Satoru, Seno, Hiroshi, Ogawa, Seishi, 90839721, 90322651, 20515514, 00789638, 40511829, 80646373, 40883707, 20772403, 70335454, 40402127, 10252462, 10379092, 90335266, Kakiuchi, Nobuyuki, Yoshida, Kenichi, Uchino, Motoi, Kihara, Takako, Akaki, Kotaro, Inoue, Yoshikage, Kawada, Kenji, Nagayama, Satoshi, Yokoyama, Akira, Yamamoto, Shuji, Matsuura, Minoru, Horimatsu, Takahiro, Hirano, Tomonori, Goto, Norihiro, Takeuchi, Yasuhide, Ochi, Yotaro, Shiozawa, Yusuke, Kogure, Yasunori, Watatani, Yosaku, Fujii, Yoichi, Kim, Soo Ki, Kon, Ayana, Kataoka, Keisuke, Yoshizato, Tetsuichi, Nakagawa, Masahiro M., Yoda, Akinori, Nanya, Yasuhito, Makishima, Hideki, Shiraishi, Yuichi, Chiba, Kenichi, Tanaka, Hiroko, Sanada, Masashi, Sugihara, Eiji, Sato, Taka-aki, Maruyama, Takashi, Miyoshi, Hiroyuki, Taketo, Makoto Mark, Oishi, Jun, Inagaki, Ryosaku, Ueda, Yutaka, Okamoto, Shinya, Okajima, Hideaki, Sakai, Yoshiharu, Sakurai, Takaki, Haga, Hironori, Hirota, Seiichi, Ikeuchi, Hiroki, Nakase, Hiroshi, Marusawa, Hiroyuki, Chiba, Tsutomu, Takeuchi, Osamu, Miyano, Satoru, Seno, Hiroshi, and Ogawa, Seishi

Abstract

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1, 2, 3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.

Published
2020

30. Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis

Author

Kakiuchi, Nobuyuki, primary, Yoshida, Kenichi, additional, Uchino, Motoi, additional, Kihara, Takako, additional, Akaki, Kotaro, additional, Inoue, Yoshikage, additional, Kawada, Kenji, additional, Nagayama, Satoshi, additional, Yokoyama, Akira, additional, Yamamoto, Shuji, additional, Matsuura, Minoru, additional, Horimatsu, Takahiro, additional, Hirano, Tomonori, additional, Goto, Norihiro, additional, Takeuchi, Yasuhide, additional, Ochi, Yotaro, additional, Shiozawa, Yusuke, additional, Kogure, Yasunori, additional, Watatani, Yosaku, additional, Fujii, Yoichi, additional, Kim, Soo Ki, additional, Kon, Ayana, additional, Kataoka, Keisuke, additional, Yoshizato, Tetsuichi, additional, Nakagawa, Masahiro M., additional, Yoda, Akinori, additional, Nanya, Yasuhito, additional, Makishima, Hideki, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Sanada, Masashi, additional, Sugihara, Eiji, additional, Sato, Taka-aki, additional, Maruyama, Takashi, additional, Miyoshi, Hiroyuki, additional, Taketo, Makoto Mark, additional, Oishi, Jun, additional, Inagaki, Ryosaku, additional, Ueda, Yutaka, additional, Okamoto, Shinya, additional, Okajima, Hideaki, additional, Sakai, Yoshiharu, additional, Sakurai, Takaki, additional, Haga, Hironori, additional, Hirota, Seiichi, additional, Ikeuchi, Hiroki, additional, Nakase, Hiroshi, additional, Marusawa, Hiroyuki, additional, Chiba, Tsutomu, additional, Takeuchi, Osamu, additional, Miyano, Satoru, additional, Seno, Hiroshi, additional, and Ogawa, Seishi, additional

Published
2019
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31. PPM1D and DNMT3A Mutations in Myelodysplasia and Clonal Hematopoiesis

Author

Motomura, Masanori, primary, Inoue, Yoshikage, additional, Nagata, Yasunobu, additional, Yoshizato, Tetsuichi, additional, Baer, Constance, additional, Momozawa, Yukihide, additional, Nadarajah, Niroshan, additional, Nannya, Yasuhito, additional, Yoshida, Kenichi, additional, Haferlach, Claudia, additional, Kern, Wolfgang, additional, Atsuta, Yoshiko, additional, Iijima-Yamashita, Yuka, additional, Shiraishi, Yuichi, additional, Onizuka, Makoto, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Itonaga, Hidehiro, additional, Miyazaki, Yasushi, additional, Horibe, Keizo, additional, Sanada, Masashi, additional, Kamatani, Yoichiro, additional, Kubo, Michiaki, additional, Miyano, Satoru, additional, Haferlach, Torsten, additional, Ogawa, Seishi, additional, and Makishima, Hideki, additional

Published
2019
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32. Abstract 1683: Mutational landscape of colorectal cancer with POLE gene mutation

Author

Inoue, Yoshikage, primary, Kakiuchi, Nobuyuki, additional, Yoshida, Kenichi, additional, Shiozawa, Yusuke, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Yoshizato, Tetsuichi, additional, Tanaka, HIroko, additional, Nagayama, Satoshi, additional, Miyano, Satoru, additional, Sakai, Yoshiharu, additional, and Ogawa, Seishi, additional

Published
2019
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33. Abstract 3429: Genetic analysis of pancreatic neuroendocrine neoplasms grade 3

Author

Kakiuchi, Nobuyuki, primary, Yoshida, Kenichi, additional, Shiozawa, Yusuke, additional, Yokoyama, Akira, additional, Kataoka, Keisuke, additional, Inoue, Yoshikage, additional, Takeuchi, Yasuhide, additional, Hirano, Tomonori, additional, Fujii, Yoichi, additional, Ueno, Hiroo, additional, Hijioka, Susumu, additional, Mizuno, Nobumasa, additional, Hosoda, Waki, additional, Yatabe, Yasushi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Shiraishi, Yuichi, additional, Miyano, Satoru, additional, Masui, Toshihiko, additional, Uemoto, Shinji, additional, Yoshizawa, Akihiko, additional, Haga, Hironori, additional, Uza, Norimitsu, additional, Seno, Hiroshi, additional, Kodama, Yuzo, additional, and Ogawa, Seishi, additional

Published
2019
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34. Abstract 3322: Chronology and risk-dependence of age-related remodelling of oesophageal epithelia

Author

Yokoyama, Akira, primary, Kakiuchi, Nobuyuki, additional, Yoshizato, Tetsuichi, additional, Nannya, Yasuhito, additional, Suzuki, Hiromichi, additional, Takeuchi, Yasuhide, additional, Shiozawa, Yusuke, additional, Sato, Yusuke, additional, Aoki, Kosuke, additional, kim, Soo, additional, Fujii, Yoichi, additional, Yoshida, Kenichi, additional, Kataoka, Keisuke, additional, Nakagawa, Masahiro M., additional, Inoue, Yoshikage, additional, Hirano, Tomonori, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Sanada, Masashi, additional, Ohashi, Shinya, additional, Miyamoto, Shin’ichi, additional, Tsunoda, Shigeru, additional, Mimori, Koshi, additional, Minamiguchi, Sachiko, additional, Miyano, Satoru, additional, Makishima, Hideki, additional, Muto, Manabu, additional, and Ogawa, Seishi, additional

Published
2019
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35. Abstract 5126: Genetic analysis of metachronous pancreatic cancers

Author

Tomonori, Hirano, primary, Kakiuchi, Nobuyuki, additional, Takeuchi, Yasuhide, additional, Inoue, Yoshikage, additional, Nishimura, Tomomi, additional, Fujii, Yoichi, additional, Yokoyama, Akira, additional, Makishima, Hideki, additional, Masui, Toshihiko, additional, Uemoto, Shinji, additional, Minamiguchi, Sachiko, additional, Haga, Hironori, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Shiraishi, Yuichi, additional, Miyano, Satoru, additional, Uza, Norimitsu, additional, Kodama, Yuzo, additional, Seno, Hiroshi, additional, Chiba, Tsutomu, additional, and Ogawa, Seishi, additional

Published
2019
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38. Integrated Molecular Characterization of the Lethal Pediatric Cancer Pancreatoblastoma

Author

Isobe, Tomoya, primary, Seki, Masafumi, additional, Yoshida, Kenichi, additional, Sekiguchi, Masahiro, additional, Shiozawa, Yusuke, additional, Shiraishi, Yuichi, additional, Kimura, Shunsuke, additional, Yoshida, Misa, additional, Inoue, Yoshikage, additional, Yokoyama, Akira, additional, Kakiuchi, Nobuyuki, additional, Suzuki, Hiromichi, additional, Kataoka, Keisuke, additional, Sato, Yusuke, additional, Kawai, Tomoko, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Shimamura, Teppei, additional, Kato, Motohiro, additional, Iguchi, Akihiro, additional, Hama, Asahito, additional, Taguchi, Tomoaki, additional, Akiyama, Masaharu, additional, Fujimura, Junya, additional, Inoue, Akiko, additional, Ito, Tsuyoshi, additional, Deguchi, Takao, additional, Kiyotani, Chikako, additional, Iehara, Tomoko, additional, Hosoi, Hajime, additional, Oka, Akira, additional, Sanada, Masashi, additional, Tanaka, Yukichi, additional, Hata, Kenichiro, additional, Miyano, Satoru, additional, Ogawa, Seishi, additional, and Takita, Junko, additional

Published
2018
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39. Abstract 5754: The genetic aberrations in carcinogenic sequence of colitis-associated cancer

Author

Kakiuchi, Nobuyuki, primary, Yoshida, Kenichi, additional, Shiozawa, Yusuke, additional, Yokoyama, Akira, additional, Kataoka, Keisuke, additional, Inoue, Yoshikage, additional, Takeuchi, Yasuhide, additional, Kogure, Yasunori, additional, Kon, Ayana, additional, Nakagawa, Masahiro, additional, Chiba, Kenichi, additional, Tanaka, Hiroko, additional, Shiraishi, Yuichi, additional, Miyano, Satoru, additional, Kawada, Kenji, additional, Okajima, Hideaki, additional, Sakai, Yoshiharu, additional, Sakurai, Takaki, additional, Haga, Hironori, additional, Nakase, Hiroshi, additional, Uchino, Motoi, additional, Ikeuchi, Hiroki, additional, Kihara, Takako, additional, Hirota, Seiichi, additional, Horimatsu, Takahiro, additional, Matsuura, Minoru, additional, Marusawa, Hiroyuki, additional, Seno, Hiroshi, additional, and Ogawa, Seishi, additional

Published
2017
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40. Abstract 4385: Landscape of driver gene mutations in stage II and stage III colorectal cancer

Author

Inoue, Yoshikage, primary, Kakiuchi, Nobuyuki, additional, Yoshida, Kenichi, additional, Shiozawa, Yusuke, additional, Shiraishi, Yuichi, additional, Chiba, Kenichi, additional, Kataoka, Keisuke, additional, Ueno, Hiroo, additional, Tanaka, Hiroko, additional, Nagayama, Satoshi, additional, Miyano, Satoru, additional, Sakai, Yoshiharu, additional, and Ogawa, Seishi, additional

Published
2017
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41. Elevation-dependent behavior of hoar-prominent snowpack on forest slopes in the Japanese Central Alps based on a decade of observations.

Author

Harada, Yusuke, Wakabayashi, Ryuzo, and Inoue, Yoshikage

Subjects
SNOW accumulation, SNOW cover, ATMOSPHERIC temperature, DEPTH hoar
Abstract

Full snow-pit observations were performed on a monthly basis over ten winter seasons from 1995 to 2004, at 15 study plots spaced at 100 m elevation intervals (1300–2700 m a.s.l.) in the mountainous forest of the Japanese Central Alps. We observed 514 pits with an average depth of 1.12 m. Density measurements were taken in 2610 snow layers in total. Monthly trends indicate that snow depth has a strong linear correlation with elevation and that the mean density of snow cover has a moderate linear correlation with elevation in midwinter. Snow water equivalent can increase as a quadratic function of elevation in January and February. For this reason, the influence of overburden load and wind packing is elevation-dependent from January to February, a period when a facet-prominent snowpack existed on account of low snow and air temperatures. The density of depth hoar is greater at higher elevations than it is for rounded grains in midwinter due to densification. On forested slopes, with increasing elevation, snowfall frequency and the impact of wind upon snow increases while air temperature decreases, causing elevational variance in grain shapes. [ABSTRACT FROM AUTHOR]

Published
2019
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42. Laparoscopy endoscopy cooperative surgery for gastric plexiform fibromyxoma: a case report

Author

50322649, Inoue, Yoshikage, Gunji, Shutaro, Obama, Kazutaka, Okabe, Hiroshi, Sakai, Yoshiharu, 50322649, Inoue, Yoshikage, Gunji, Shutaro, Obama, Kazutaka, Okabe, Hiroshi, and Sakai, Yoshiharu

Abstract

[Background] Gastric submucosal tumors are commonly treated by partial resection under laparoscopy. However, the surgical resection of gastric submucosal tumors sometimes causes deformation of the stomach, especially in the case of intraluminal tumors located near the pylorus or esophagogastric junction. Such deformations can result in impaired diet intake and reduced quality of life. Laparoscopic endoscopic cooperative surgery has been developed to overcome these problems. This is the first report to describe a case of gastric plexiform fibromyxoma, a rare gastric submucosal tumor, that was successfully resected by laparoscopic endoscopic cooperative surgery. [Case presentation] A 36-year-old Japanese woman presented with epigastric pain and anemia. Gastrointestinal endoscopy revealed a submucosal tumor in the gastric antrum. Because a definitive diagnosis could not be obtained and the tumor was located near the pylorus, we performed laparoscopic endoscopic cooperative surgery as diagnostic therapy. The postoperative course was favorable with no complications, such as delayed gastric emptying or outlet obstruction. The tumor was pathologically diagnosed as gastric plexiform fibromyxoma. [Conclusions] Laparoscopic endoscopic cooperative surgery is a useful approach for diagnostic therapy for rare submucosal tumors to avoid the deformation of the stomach, especially when the tumor is located near the pylorus.

Published
2016

43. Abstract 3213: Induction chemotherapy for stage 4 gastric cancer and prognostic molecular markers

Author

Ueda, Shugo, primary, Hattori, Kengo, additional, Inoue, Yoshikage, additional, Kadono, Kentaro, additional, Yoshimura, Mio, additional, Yoshida, Masahiro, additional, Yoshitomi, Mami, additional, Nomura, Akinari, additional, Hashida, Hiroki, additional, Terajima, Hiroaki, additional, Ozaki, Nobuhiro, additional, and Fukushima, Masakazu, additional

Published
2011
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44. PPM1Dand DNMT3AMutations in Myelodysplasia and Clonal Hematopoiesis

Author

Motomura, Masanori, Inoue, Yoshikage, Nagata, Yasunobu, Yoshizato, Tetsuichi, Baer, Constance, Momozawa, Yukihide, Nadarajah, Niroshan, Nannya, Yasuhito, Yoshida, Kenichi, Haferlach, Claudia, Kern, Wolfgang, Atsuta, Yoshiko, Iijima-Yamashita, Yuka, Shiraishi, Yuichi, Onizuka, Makoto, Chiba, Kenichi, Tanaka, Hiroko, Itonaga, Hidehiro, Miyazaki, Yasushi, Horibe, Keizo, Sanada, Masashi, Kamatani, Yoichiro, Kubo, Michiaki, Miyano, Satoru, Haferlach, Torsten, Ogawa, Seishi, and Makishima, Hideki

Abstract

Introduction:Age-related clonal hematopoiesis (CH) has been implicated in an increased risk of myeloid neoplasms. While common driver genes mutated in CH largely overlap to those in myeloid neoplasms, a notable exception is protein phosphatase Mg2+/Mn2+dependent 1D gene (PPM1D), encoding a p53-targeting phosphatase. Although it is known to be involved in DNA damage response pathways and more frequently mutated in therapy-related myeloid neoplasms than in primary ones, its role in CH and myeloid neoplasms has not been fully understood.

Published
2019
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45. Unbiased Detection of Driver Mutations in Extramammary Paget Disease.

Author

Ishida Y, Kakiuchi N, Yoshida K, Inoue Y, Irie H, Kataoka TR, Hirata M, Funakoshi T, Matsushita S, Hata H, Uchi H, Yamamoto Y, Fujisawa Y, Fujimura T, Saiki R, Takeuchi K, Shiraishi Y, Chiba K, Tanaka H, Otsuka A, Miyano S, Kabashima K, and Ogawa S

Subjects
Gene Amplification, Humans, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local pathology, Paget Disease, Extramammary metabolism, Paget Disease, Extramammary pathology, Prognosis, Receptor, ErbB-2 genetics, Survival Rate, Exome Sequencing, Biomarkers, Tumor genetics, DNA Copy Number Variations, Mutation, Neoplasm Recurrence, Local genetics, Paget Disease, Extramammary genetics, Receptor, ErbB-2 metabolism
Abstract

Purpose: Extramammary Paget disease (EMPD) is an uncommon skin malignancy whose genetic alterations are poorly characterized. Previous reports identified mutations in chromatin remodeling genes and PIK3CA . In order to unambiguously determine driver mutations in EMPD, we analyzed 87 EMPD samples using exome sequencing in combination with targeted sequencing., Experimental Design: First, we analyzed 37 EMPD samples that were surgically resected using whole-exome sequencing. Based on several in silico analysis, we built a custom capture panel of putative driver genes and analyzed 50 additional formalin-fixed, paraffin-embedded samples using target sequencing. ERBB2 expression was evaluated by HER2 immunohisotochemistry. Select samples were further analyzed by fluorescence in situ hybridization., Results: A median of 92 mutations/sample was identified in exome analysis. A union of driver detection algorithms identified ERBB2, ERBB3, KMT2C, TP53, PIK3CA, NUP93, AFDN , and CUX1 as likely driver mutations. Copy-number alteration analysis showed regions spanning CDKN2A as recurrently deleted, and ERBB2 as recurrently amplified. ERBB2, ERBB3 , and FGFR1 amplification/mutation showed tendency toward mutual exclusivity. Copy-number alteration load was associated with likelihood to recur. Mutational signatures were dominated by aging and APOBEC activation and lacked evidence of ultraviolet radiation. HER2 IHC/fluorescence in situ analysis validated ERBB2 amplification but was underpowered to detect mutations. Tumor heterogeneity in terms of ERBB2 amplification status was observed in some cases., Conclusions: Our comprehensive, unbiased analysis shows EMPD is characterized by alterations involving the PI3K-AKT pathway. EMPD is distinct from other skin cancers in both molecular pathways altered and etiology behind mutagenesis., (©2020 American Association for Cancer Research.)

Published
2021
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46. [Hepatic resection for local recurrence after radiofrequency ablation therapy for colorectal liver metastases].

Author

Iwamura S, Iida T, Terajima H, Matsubara H, Goto T, Inoue Y, Yoshitomi M, Uchida Y, Ueda S, and Kanazawa A

Subjects
Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Catheter Ablation, Colonic Neoplasms drug therapy, Colonic Neoplasms surgery, Combined Modality Therapy, Female, Humans, Liver Neoplasms drug therapy, Liver Neoplasms secondary, Male, Middle Aged, Recurrence, Treatment Outcome, Colonic Neoplasms pathology, Liver Neoplasms surgery
Abstract

Patients who underwent hepatic resection of locally recurrent tumors after radiofrequency ablation(RFA)for colorectal liver metastases (CRLM) were retrospectively investigated. Among 12 patients who underwent RFA as first-line treatment for CRLM, 7 experienced local recurrence, 5 of whom (6 nodules) underwent hepatic resection. The mean diameter (range) of the tumors was 9.5(5-16) mm, and they were located at S2, S7 (adjacent to the right hepatic vein), S5/6 (between the root of the anterior and the posterior Glisson's pedicle), S1r (right paracaval portion), S6, and S3. No local recurrence was observed after hepatic resection. In conclusion, hepatic resection must be the initial therapeutic strategy for CRLM, and the indication for RFA must be considered carefully.

Published
2014

47. [A case of lung metastases of carcinoma of the ampulla of vater effectively treated with S-1].

Author

Hashida H, Inoue Y, Hattori K, Kadono K, Yoshimura M, Yoshida M, Abe S, Miyake M, Yoshitomi M, Nomura A, Ueda S, Terajima H, and Osaki N

Subjects
Aged, Common Bile Duct Neoplasms pathology, Common Bile Duct Neoplasms surgery, Drug Combinations, Duodenal Neoplasms pathology, Duodenal Neoplasms surgery, Female, Humans, Lung Neoplasms secondary, Pancreatic Neoplasms pathology, Pancreatic Neoplasms surgery, Tomography, X-Ray Computed, Ampulla of Vater, Antimetabolites, Antineoplastic therapeutic use, Common Bile Duct Neoplasms drug therapy, Duodenal Neoplasms drug therapy, Lung Neoplasms drug therapy, Oxonic Acid therapeutic use, Pancreatic Neoplasms drug therapy, Tegafur therapeutic use
Abstract

A 70-year-old female patient underwent pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater in March 2007. In April 2009, multiple lung metastases were detected by CT scanning. The patient was treated with S-1 (80mg/day, day 1-28, followed by 2-weeks withdrawal)from April 2009. The shrinkage of lung metastases was diagnosed as a complete response based on the Response Evaluation Criteria in Solid Tumors(RECIST). No severe toxicities were observed. S-1 is an effective and safe anti-cancer agent available for lung metastases of carcinoma of the ampulla of Vater.

Published
2012

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