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2. Exercise Suppresses Head and Neck Squamous Cell Carcinoma Growth via Oncostatin M

Author

Yoshimura, Takuya, primary, Hirano, Yuka, additional, Hamada, Taiji, additional, Yokoyama, Seiya, additional, Suzuki, Hajime, additional, Takayama, Hirotaka, additional, Migita, Hirono, additional, Ishida, Takayuki, additional, Nakamura, Yasunori, additional, Ohsawa, Masahiro, additional, Asakawa, Akihiro, additional, Ishihata, Kiyohide, additional, and Tanimoto, Akihide, additional

Published
2024
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5. One-hundred-nm-scale electronic structure and transport calculations of organic polymers on the K computer

Author

Imachi, Hiroto, Yokoyama, Seiya, Kaji, Takami, Abe, Yukiya, Tada, Tomofumi, and Hoshi, Takeo

Subjects
Condensed Matter - Materials Science
Abstract

One-hundred-nm-scale electronic structure calculations were carried out on the K supercomputer by our original simulation code ELSES (http://www.elses.jp/) The present paper reports preliminary results of transport calculations for condensed organic polymers. Large-scale calculations are realized by novel massively parallel order-N algorithms. The transport calculations were carried out as a theoretical extension for the quantum wavepacket dynamics simulation. The method was applied to a single polymer chain and condensed polymers., Comment: 4 pages, 2 figures

Published
2016
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7. Novel linear algebraic theory and one-hundred-million-atom quantum material simulations on the K computer

Author

Hoshi, Takeo, Sogabe, Tomohiro, Miyatad, Takafumi, Lee, Dongjin, Zhang, Shao-Liang, Imachi, Hiroto, Kawai, Yoshifumi, Akiyama, Yohei, Yamazaki, Keita, and Yokoyama, Seiya

Subjects
Condensed Matter - Materials Science, Physics - Computational Physics
Abstract

The present paper gives a review of our recent progress and latest results for novel linear-algebraic algorithms and its application to large-scale quantum material simulations or electronic structure calculations. The algorithms are Krylov-subspace (iterative) solvers for generalized shifted linear equations, in the form of (zS-H)x=b,in stead of conventional generalized eigen-value equation. The method was implemented in our order-$N$ calculation code ELSES (http://www.elses.jp/) with modelled systems based on ab initio calculations. The code realized one-hundred-million-atom, or 100-nm-scale, quantum material simulations on the K computer in a high parallel efficiency with up to all the built-in processor cores. The present paper also explains several methodological aspects, such as use of XML files and 'novice' mode for general users. A sparse matrix data library in our real problems (http://www.elses.jp/matrix/) was prepared. Internal eigen-value problem is discussed as a general need from the quantum material simulation. The present study is a interdisciplinary one and is sometimes called 'Application-Algorithm-Architecture co-design'. The co-design will play a crucial role in exa-scale scientific computations., Comment: 13 pages, 6 figures

Published
2014

9. Characterization and treatment of gemcitabine‐ and cisplatin‐resistant bladder cancer cells with a pan‐RAS inhibitor

Author

Yoshino, Hirofumi, primary, Yokoyama, Seiya, additional, Tamai, Motoki, additional, Okamura, Shunsuke, additional, Iizasa, Sayaka, additional, Sakaguchi, Takashi, additional, Osako, Yoichi, additional, Inoguchi, Satoru, additional, Matsushita, Ryosuke, additional, Yamada, Yasutoshi, additional, Nakagawa, Masayuki, additional, Tatarano, Shuichi, additional, Tanimoto, Akihide, additional, and Enokida, Hideki, additional

Published
2023
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11. Favorable prognostic impact of phosphatase and tensin homolog alterations in wild-type isocitrate dehydrogenase and telomerase reverse transcriptase promoter glioblastoma

Author

Higa, Nayuta, primary, Akahane, Toshiaki, additional, Yokoyama, Seiya, additional, Makino, Ryutaro, additional, Yonezawa, Hajime, additional, Uchida, Hiroyuki, additional, Takajo, Tomoko, additional, Kirishima, Mari, additional, Hamada, Taiji, additional, Noguchi, Naoki, additional, Otsuji, Ryosuke, additional, Kuga, Daisuke, additional, Nagasaka, Shohei, additional, Yamahata, Hitoshi, additional, Yamamoto, Junkoh, additional, Yoshimoto, Koji, additional, Tanimoto, Akihide, additional, and Hanaya, Ryosuke, additional

Published
2023
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13. Identification of Neck Lymph Node Metastasis-Specific microRNA—Implication for Use in Monitoring or Prediction of Neck Lymph Node Metastasis.

Author

Higashi, Yutaro, Nakamura, Kodai, Takaoka, Ryota, Tani, Mika, Noma, Yusaku, Mori, Kazuki, Yamashiro, Kota, Yokoyama, Seiya, Hamada, Tomofumi, and Sugiura, Tsuyoshi

Subjects
HEAD & neck cancer diagnosis, METASTASIS, LYMPH nodes, MICRORNA, HEAD & neck cancer, REGRESSION analysis, CANCER patients, COMPARATIVE studies, DESCRIPTIVE statistics, RESEARCH funding, TUMOR markers, POLYMERASE chain reaction, SENSITIVITY & specificity (Statistics), SQUAMOUS cell carcinoma
Abstract

Simple Summary: There are no established biomarkers for oral squamous cell carcinoma (OSCC), and detection of neck lymph node metastases relies on imaging studies. Diagnosis and prediction using biomarkers, which are less invasive and simpler than imaging tests, could improve prognosis if lymph node metastases could be treated earlier. In this study, serum microRNAs were successfully used to diagnose primary neck lymph node metastases and predict late neck lymph node metastases. They reflected the presence of lymph node metastasis more accurately than serum squamous cell carcinoma antigens or pathological factors. MicroRNAs (miRNAs) have attracted attention as non-invasive cancer biomarkers in various cancers; however, they have not been adequately investigated in oral squamous cell carcinoma (OSCC). This study investigated the diagnostic performance of serum-derived miRNAs at initial diagnosis for primary neck lymph node metastasis and the predictive performance for late neck lymph node metastasis based on long-term (up to approximately 8 years) follow-up of patients with OSCC. The expression of miRNAs in 40 patients with OSCC was quantified using real-time PCR (qPCR), and a comprehensive statistical analysis of the correlation of miRNA expression for primary and late neck lymph node metastases was performed. For the diagnosis of primary neck lymph node metastases, miR-423 and miR-125 were accurate. The miRNA index for primary metastasis diagnosis (miR-PM) calculated by regression analysis showed high diagnostic accuracy. The miR-5100 was useful for predicting late neck lymph node metastases. The miRNA index for late metastasis prediction (miR-LM) calculated using regression analysis showed high prediction accuracy. MiRNAs were useful for diagnosing primary neck lymph node metastases in OSCC and predicting late neck lymph node metastases. It may help to consider individualized treatment, including follow-up, surgical methods, and postoperative management. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Molecular Genetic Profile of 300 Japanese Patients with Diffuse Gliomas Using a Glioma-tailored Gene Panel

Author

HIGA, Nayuta, primary, AKAHANE, Toshiaki, additional, YOKOYAMA, Seiya, additional, YONEZAWA, Hajime, additional, UCHIDA, Hiroyuki, additional, FUJIO, Shingo, additional, KIRISHIMA, Mari, additional, TAKIGAWA, Kosuke, additional, HATA, Nobuhiro, additional, TOH, Keita, additional, YAMAMOTO, Junkoh, additional, HANAYA, Ryosuke, additional, TANIMOTO, Akihide, additional, and YOSHIMOTO, Koji, additional

Published
2022
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15. Distribution and favorable prognostic implication of genomicEGFRalterations inIDH‐wildtype glioblastoma

Author

Higa, Nayuta, primary, Akahane, Toshiaki, additional, Hamada, Taiji, additional, Yonezawa, Hajime, additional, Uchida, Hiroyuki, additional, Makino, Ryutaro, additional, Watanabe, Shoji, additional, Takajo, Tomoko, additional, Yokoyama, Seiya, additional, Kirishima, Mari, additional, Matsuo, Kei, additional, Fujio, Shingo, additional, Hanaya, Ryosuke, additional, Tanimoto, Akihide, additional, and Yoshimoto, Koji, additional

Published
2022
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16. Genome Editing Using Cas9 Ribonucleoprotein Is Effective for Introducing PDGFRA Variant in Cultured Human Glioblastoma Cell Lines.

Author

Hamada, Taiji, Yokoyama, Seiya, Akahane, Toshiaki, Matsuo, Kei, and Tanimoto, Akihide

Subjects
*GENOME editing, *CRISPRS, *CELL lines, *PLASMIDS, *PLATELET-derived growth factor receptors, *CANCER cell analysis
Abstract

Many variants of uncertain significance (VUS) have been detected in clinical cancer cases using next-generation sequencing-based cancer gene panel analysis. One strategy for the elucidation of VUS is the functional analysis of cultured cancer cell lines that harbor targeted gene variants using genome editing. Genome editing is a powerful tool for creating desired gene alterations in cultured cancer cell lines. However, the efficiency of genome editing varies substantially among cell lines of interest. We performed comparative studies to determine the optimal editing conditions for the introduction of platelet-derived growth factor receptor alpha (PDGFRA) variants in human glioblastoma multiforme (GBM) cell lines. After monitoring the copy numbers of PDGFRA and the expression level of the PDGFRα protein, four GBM cell lines (U-251 MG, KNS-42, SF126, and YKG-1 cells) were selected for the study. To compare the editing efficiency in these GBM cell lines, the modes of clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) delivery (plasmid vs. ribonucleoprotein (RNP)), methods of transfection (lipofection vs. electroporation), and usefulness of cell sorting were then evaluated. Herein, we demonstrated that electroporation-mediated transfer of Cas9 with single-guide RNA (Cas9 RNP complex) could sufficiently edit a target nucleotide substitution, irrespective of cell sorting. As the Cas9 RNP complex method showed a higher editing efficiency than the Cas9 plasmid lipofection method, it was the optimal method for single-nucleotide editing in human GBM cell lines under our experimental conditions. [ABSTRACT FROM AUTHOR]

Published
2023
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17. Distribution and favorable prognostic implication of genomic EGFR alterations in IDH‐wildtype glioblastoma.

Author

Higa, Nayuta, Akahane, Toshiaki, Hamada, Taiji, Yonezawa, Hajime, Uchida, Hiroyuki, Makino, Ryutaro, Watanabe, Shoji, Takajo, Tomoko, Yokoyama, Seiya, Kirishima, Mari, Matsuo, Kei, Fujio, Shingo, Hanaya, Ryosuke, Tanimoto, Akihide, and Yoshimoto, Koji

Subjects
EPIDERMAL growth factor receptors, PROGNOSIS, ISOCITRATE dehydrogenase, GLIOBLASTOMA multiforme
Abstract

Background: We aimed to evaluate the mutation profile, transcriptional variants, and prognostic impact of the epidermal growth factor receptor (EGFR) gene in isocitrate dehydrogenase (IDH)‐wildtype glioblastomas (GBMs). Methods: We sequenced EGFR, evaluated the EGFR splicing profile using a next‐generation sequencing oncopanel, and analyzed the outcomes in 138 grade IV IDH‐wildtype GBM cases. Results: EGFR mutations were observed in 10% of GBMs. A total of 23.9% of the GBMs showed EGFR amplification. Moreover, 25% of the EGFR mutations occurred in the kinase domain. Notably, EGFR alterations were a predictor of good prognosis (p = 0.035). GBM with EGFR alterations was associated with higher Karnofsky Performance Scale scores (p = 0.014) and lower Ki‐67 scores (p = 0.005) than GBM without EGFR alterations. EGFRvIII positivity was detected in 21% of EGFR‐amplified GBMs. We identified two other EGFR variants in GBM cases with deletions of exons 6–7 (Δe 6–7) and exons 2–14 (Δe 2–14). In one case, the initial EGFRvIII mutation transformed into an EGFR Δe 2–14 mutation during recurrence. Conclusions: We found that the EGFR gene profiles of GBM differ among cohorts and that EGFR alterations are good prognostic markers of overall survival in patients with IDH‐wildtype GBM. Additionally, we identified rare EGFR variants with longitudinal and temporal transformations of EGFRvIII. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma

Author

Higa, Nayuta, primary, Akahane, Toshiaki, additional, Yokoyama, Seiya, additional, Yonezawa, Hajime, additional, Uchida, Hiroyuki, additional, Takajo, Tomoko, additional, Otsuji, Ryosuke, additional, Hamada, Taiji, additional, Matsuo, Kei, additional, Kirishima, Mari, additional, Hata, Nobuhiro, additional, Hanaya, Ryosuke, additional, Tanimoto, Akihide, additional, and Yoshimoto, Koji, additional

Published
2022
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19. Molecular Evaluation of Endometrial Dedifferentiated Carcinoma, Endometrioid Carcinoma, Carcinosarcoma, and Serous Carcinoma Using a Custom-Made Small Cancer Panel

Author

Kobayashi, Yusuke, primary, Kitazono, Ikumi, additional, Akahane, Toshiaki, additional, Yanazume, Shintaro, additional, Kamio, Masaki, additional, Togami, Shinichi, additional, Nohara, Sachio, additional, Sakamoto, Ippei, additional, Yokoyama, Seiya, additional, Tabata, Kazuhiro, additional, Kobayashi, Hiroaki, additional, and Tanimoto, Akihide, additional

Published
2021
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22. A tailored next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas

Author

Higa, Nayuta, primary, Akahane, Toshiaki, additional, Yokoyama, Seiya, additional, Yonezawa, Hajime, additional, Uchida, Hiroyuki, additional, Takajo, Tomoko, additional, Kirishima, Mari, additional, Hamada, Taiji, additional, Matsuo, Kei, additional, Fujio, Shingo, additional, Hanada, Tomoko, additional, Hosoyama, Hiroshi, additional, Yonenaga, Masanori, additional, Sakamoto, Akihisa, additional, Hiraki, Tsubasa, additional, Tanimoto, Akihide, additional, and Yoshimoto, Koji, additional

Published
2020
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24. Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning

Author

Yokoyama, Seiya, primary, Hamada, Taiji, additional, Higashi, Michiyo, additional, Matsuo, Kei, additional, Maemura, Kosei, additional, Kurahara, Hiroshi, additional, Horinouchi, Michiko, additional, Hiraki, Tsubasa, additional, Sugimoto, Tomoyuki, additional, Akahane, Toshiaki, additional, Yonezawa, Suguru, additional, Kornmann, Marko, additional, Batra, Surinder K., additional, Hollingsworth, Michael A., additional, and Tanimoto, Akihide, additional

Published
2020
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25. The application of methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5' CpG island of mucin in cancer cells

Author

Yokoyama Seiya, Kitamoto Sho, Yamada Norishige, Houjou Izumi, Sugai Tamotsu, Nakamura Shin-ichi, Arisaka Yoshifumi, Takaori Kyoichi, Higashi Michiyo, and Yonezawa Suguru

Subjects
DNA methylation pattern, Epigenetics, Mucin, Colonic crypt, Pancreatic juice, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Methylation of CpG sites in genomic DNA plays an important role in gene regulation and especially in gene silencing. We have reported mechanisms of epigenetic regulation for expression of mucins, which are markers of malignancy potential and early detection of human neoplasms. Epigenetic changes in promoter regions appear to be the first step in expression of mucins. Thus, detection of promoter methylation status is important for early diagnosis of cancer, monitoring of tumor behavior, and evaluating the response of tumors to targeted therapy. However, conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity. Methods Here, we report a modified version of the bisulfite-DGGE (denaturing gradient gel electrophoresis) using a nested PCR approach. We designated this method as methylation specific electrophoresis (MSE). The MSE method is comprised of the following steps: (a) bisulfite treatment of genomic DNA, (b) amplification of the target DNA by a nested PCR approach and (c) applying to DGGE. To examine whether the MSE method is able to analyze DNA methylation of mucin genes in various samples, we apply it to DNA obtained from state cell lines, ethanol-fixed colonic crypts and human pancreatic juices. Result The MSE method greatly decreases the amount of input DNA. The lower detection limit for distinguishing different methylation status is < 0.1% and the detectable minimum amount of DNA is 20 pg, which can be obtained from only a few cells. We also show that MSE can be used for analysis of challenging samples such as human isolated colonic crypts or human pancreatic juices, from which only a small amount of DNA can be extracted. Conclusions The MSE method can provide a qualitative information of methylated sequence profile. The MSE method allows sensitive and specific analysis of the DNA methylation pattern of almost any block of multiple CpG sites. The MSE method can be applied to analysis of DNA methylation status in many different clinical samples, and this may facilitate identification of new risk markers.

Published
2012
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27. Immunohistochemical expression of mucin antigens in gallbladder adenocarcinoma: MUC1-positive and MUC2-negative expression is associated with vessel invasion and shortened survival

Author

Hiraki, Tsubasa, Yamada, Sohsuke, Higashi, Michiyo, Hatanaka, Kazuhito, Yokoyama, Seiya, Kitazono, Ikumi, Goto, Yuko, Kirishima, Mari, Batra, Surinder K., Yonezawa, Suguru, and Tanimoto, Akihide

Subjects
Vessel invasion, MUC2, 6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología [CDU], Disease specific survival, MUC1, Gallbladder adenocarcinoma (GBAC)
Abstract

Mucins play pivotal roles in influencing cancer biology, for example affecting carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to investigate the significance of expression profiles of two mucins in particular, MUC1 and MUC2, their correlations with various clinicopathological features, and prognosis in gallbladder adenocarcinoma (GBAC). We performed immunohistochemistry from patients with surgically resected GBAC, using antibodies against mucin core proteins MUC1/DF3 and MUC2/Ccp58 in 81 paraffin-embedded tumor samples. MUC1 or MUC2 expression was considered to be high when ≥20% or 10% of the GBAC cells showed positive staining, respectively. High MUC1 expression was revealed to have a significant relationship to the presence of pathologically lymphatic and vascular invasion, and regional lymph node metastasis. By contrast, high MUC2 expression showed a significant correlation with pathologically perineural invasion, T stage ≥3, and post-operative recurrence. Moreover, MUC1 showed significantly positive co-expression and potentially complementary correlations with MUC2. Multivariate analyses demonstrated that the high MUC1 expression group had significantly shorter diseasespecific survival times. However, the combination of both high MUC1 and MUC2 expression did not predict worse outcome in GBACs. Therefore, although each mucin has a somewhat important role in the pathogenesis of GBAC progression, MUC1 can independently predict vessel invasion and poor prognosis in patients with GBAC. The detection of MUC1 might well offer a useful parameter for providing clinical management and treatment against postsurgical GBACs.

Published
2017

31. Significant photoresponsivity enhancement of polycrystalline BaSi2 films formed on heated Si(111) substrates by sputtering

Author

Matsuno, Satoshi, Takabe, Ryota, Yokoyama, Seiya, Toko, Kaoru, Mesuda, Masami, Kuramochi, Hideto, and Suemasu, Takashi

Abstract

We fabricated approximately 200-nm-thick BaSi2 films on Si(111) substrates at 600 °C. The formation of BaSi2 was demonstrated by X-ray diffraction and Raman spectroscopy. A reduction in the electron concentration (n = 2 × 1016 cm−3) by 3 orders of magnitude compared to that previously reported (n = 7 × 1019 cm−3) and resultant photoresponsivity enhancement by more than two orders of magnitude were achieved. The photoresponsivity increased with the bias voltage V bias applied between the top and bottom electrodes, and reached approximately 0.19 A/W at 2.0 eV, room temperature, and |V bias| = 0.5 V.

Published
2018

32. TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer

Author

Yokoyama, Seiya, primary, Higashi, Michiyo, additional, Tsutsumida, Hideaki, additional, Wakimoto, Jouji, additional, Hamada, Tomofumi, additional, Wiest, Edwin, additional, Matsuo, Kei, additional, Kitazono, Ikumi, additional, Goto, Yuko, additional, Guo, Xin, additional, Hamada, Taiji, additional, Yamada, Sohsuke, additional, Hiraki, Tsubasa, additional, Yonezawa, Suguru, additional, Batra, Surinder K., additional, Hollingsworth, Michael A., additional, and Tanimoto, Akihide, additional

Published
2017
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33. Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas

Author

Yokoyama, Seiya, primary, Higashi, Michiyo, additional, Kitamoto, Sho, additional, Oeldorf, Monika, additional, Knippschild, Uwe, additional, Kornmann, Marko, additional, Maemura, Kosei, additional, Kurahara, Hiroshi, additional, Wiest, Edwin, additional, Hamada, Tomofumi, additional, Kitazono, Ikumi, additional, Goto, Yuko, additional, Tasaki, Takashi, additional, Hiraki, Tsubasa, additional, Hatanaka, Kazuhito, additional, Mataki, Yuko, additional, Taguchi, Hiroki, additional, Hashimoto, Shinichi, additional, Batra, Surinder K., additional, Tanimoto, Akihide, additional, Yonezawa, Suguru, additional, and Hollingsworth, Michael A., additional

Published
2016
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34. A Comprehensive Expression Analysis of Mucins in Appendiceal Carcinoma in a Multicenter Study: MUC3 Is a Novel Prognostic Factor

Author

Shibahara, Hiroaki, primary, Higashi, Michiyo, additional, Yokoyama, Seiya, additional, Rousseau, Karine, additional, Kitazono, Iwao, additional, Osako, Masahiko, additional, Shirahama, Hiroshi, additional, Tashiro, Yukie, additional, Kurumiya, Yasuhiro, additional, Narita, Michihiko, additional, Kuze, Shingo, additional, Hasagawa, Hiroshi, additional, Kato, Takehito, additional, Kubota, Hitoshi, additional, Suzuki, Hideaki, additional, Arai, Toshiyuki, additional, Sakai, Yu, additional, Yuasa, Norihiro, additional, Fujino, Masahiko, additional, Kondo, Shinji, additional, Okamoto, Yoshichika, additional, Yamamoto, Tatsuyoshi, additional, Hiromatsu, Takashi, additional, Sasaki, Eiji, additional, Shirai, Kazuhisa, additional, Kawai, Satoru, additional, Hattori, Koutarou, additional, Tsuji, Hideki, additional, Okochi, Osamu, additional, Sakamoto, Masaki, additional, Kondo, Akinobu, additional, Konishi, Naomi, additional, Batra, Surinder K., additional, and Yonezawa, Suguru, additional

Published
2014
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36. Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer

Author

Shibahara, Hiroaki, primary, Higashi, Michiyo, additional, Koriyama, Chihaya, additional, Yokoyama, Seiya, additional, Kitazono, Iwao, additional, Kurumiya, Yasuhiro, additional, Narita, Michihiko, additional, Kuze, Shingo, additional, Kyokane, Takanori, additional, Mita, Saburo, additional, Arai, Toshiyuki, additional, Kato, Takehito, additional, Yuasa, Norihiro, additional, Yamaguchi, Ryuzo, additional, Kubota, Hitoshi, additional, Suzuki, Hideaki, additional, Baba, Satoshi, additional, Rousseau, Karine, additional, Batra, Surinder K., additional, and Yonezawa, Suguru, additional

Published
2014
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37. Diagnosis of Pancreatic Neoplasms Using a Novel Method of DNA Methylation Analysis of Mucin Expression in Pancreatic Juice

Author

Yokoyama, Seiya, primary, Kitamoto, Sho, additional, Higashi, Michiyo, additional, Goto, Yuko, additional, Hara, Taro, additional, Ikebe, Dai, additional, Yamaguchi, Taketo, additional, Arisaka, Yoshifumi, additional, Niihara, Toru, additional, Nishimata, Hiroto, additional, Tanaka, Sadao, additional, Takaori, Kyoichi, additional, Batra, Surinder K., additional, and Yonezawa, Suguru, additional

Published
2014
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38. MUC4 and MUC1 Expression in Adenocarcinoma of the Stomach Correlates with Vessel Invasion and Lymph Node Metastasis: An Immunohistochemical Study of Early Gastric Cancer

Author

Tamura, Yukihiro, primary, Higashi, Michiyo, additional, Kitamoto, Sho, additional, Yokoyama, Seiya, additional, Osako, Masahiko, additional, Horinouchi, Michiko, additional, Shimizu, Takeshi, additional, Tabata, Mineo, additional, Batra, Surinder K., additional, Goto, Masamichi, additional, and Yonezawa, Suguru, additional

Published
2012
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43. Molecular Evaluation of Endometrial Dedifferentiated Carcinoma, Endometrioid Carcinoma, Carcinosarcoma, and Serous Carcinoma Using a Custom-Made Small Cancer Panel.

Author

Kobayashi Y, Kitazono I, Akahane T, Yanazume S, Kamio M, Togami S, Nohara S, Sakamoto I, Yokoyama S, Tabata K, Kobayashi H, and Tanimoto A

Subjects
Aged, Aged, 80 and over, Carcinoma genetics, Carcinoma pathology, Carcinosarcoma genetics, Carcinosarcoma pathology, Endometrial Neoplasms genetics, Endometrial Neoplasms pathology, Female, High-Throughput Nucleotide Sequencing, Humans, Middle Aged, Sequence Analysis, DNA, Carcinoma classification, Carcinosarcoma classification, Endometrial Neoplasms classification
Abstract

It is often difficult to histologically differentiate among endometrial dedifferentiated carcinoma (DC), endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma (CS) due to the presence of solid components. In this study, we aimed to categorize these carcinomas according to The Cancer Genome Atlas (TCGA) classification using a small custom-made cancer genome panel (56 genes and 17 microsatellite regions) for integrated molecular diagnosis. A total of 36 endometrial cancer cases with solid components were assessed using IHC, next-generation sequencing (NGS), and the custom-made panel. Among 19 EC cases, six were categorized as MMR-deficient (MMR-d) and eight were classified as having a nonspecific molecular profile. Three EC cases were classified as POLE mutation ( POLE mut)-type, which had a very high tumor mutation burden (TMB) and low microsatellite instability (MSI). Increased TMB and MSI were observed in all three DC cases, classified as MMR-d with mutations in MLH1 and POLD1 . Except for one case classified as MMR-d, all SC cases exhibited TP53 mutations and were classified as p53 mutation-type. SC cases also exhibited amplification of CCND1 , CCNE1 , and MYC . CS cases were classified as three TCGA types other than the POLE mut-type. The IHC results for p53 and ARID1A were almost consistent with their mutation status. NGS analysis using a small panel enables categorization of endometrial cancers with solid proliferation according to TCGA classification. As TCGA molecular classification does not consider histological findings, an integrated analytical procedure including IHC and NGS may be a practical diagnostic tool for endometrial cancers., Competing Interests: SN and IS are employed by Mitsubishi Space Software. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kobayashi, Kitazono, Akahane, Yanazume, Kamio, Togami, Nohara, Sakamoto, Yokoyama, Tabata, Kobayashi and Tanimoto.)

Published
2021
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