Annual Report 2022

Division of Molecular Pathology

Yasushi Yatabe, Nobuyoshi Hiraoka, Shigeki Sekine, Taisuke Mori, Yoshihisa Kobayashi, Makoto Hirata, Taiki Hashimoto, Takako Ishiyama, Reiko Ogawa, Chie Naito, Masanori Fuse, Eijitu Ryo, Akane Sei, Melvin Pan, Chika Takeuchi Richter, Harumi Koguchi, Erika, Kawasaki, Yukiko Nakamura, Jumpei Kashima, Toshihide Hirai, Yuji Muraoka, Airi Sakyo, Sachiyo Hasegawa, Nozomi Handa

Introduction

 Morphological analysis is one of the oldest fields in cancer research; thus this field covers a wide range of knowledge that has been developed for several decades. The Division of Molecular Pathology aims to integrate this knowledge with the rapidly evolving field of molecular biology to study the molecular biological characteristics of tumors from the morphological perspective.

The Team and What We Do

 Diagnosis is now made on the basis of various protein expressions and genetic abnormalities that go beyond morphology, and drugs that are highly effective against specific genetic mutations have been developed for some tumors. In the field of molecular pathology, we collaborate closely with the Department of Diagnostic Pathology of the National Cancer Center Hospital, and conduct research on the use of genetic alterations in diagnosis and identification of genetic abnormalities that are useful in diagnosis, based on the questions raised in the diagnostic process. We are also investigating the molecular mechanisms of tumorigenesis and progression based on the results of various biologic research projects and cancer genome medicine.

Research Activities

 Lung cancer: We published an ESMO expert consensus statement on genetic analysis and treatment of EGFR-positive non-small cell lung cancer, including the perioperative period, and an ATORG (Asian Thoracic Oncology Research Group) expert consensus statement on diagnostic and therapeutic considerations of MET alterations in NSCLC. We also published the results of several studies, such as reports on the correlation of histological grade with genotypes and clinical outcomes in lung adenocarcinoma, INSM1 expression in thymoma and genetic analysis of mucinous nodules in invasive mucinous adenocarcinoma.

 Gastrointestinal cancer: We are analyzing the molecular abnormalities involved in the developmental process of gastrointestinal cancers. In particular, we are focusing on the serrated pathway in colorectal cancer, which is a different carcinogenic pathway from the adenoma-carcinoma sequence. We recently have reported on serrated lesions in familial adenomatous colorectal adenomatous carcinomatosis, including analysis of the carcinogenic process via superficially serrated adenoma, a new serrated lesion we have proposed.

 Head and neck cancer: We performed TP53 sequencing of 126 pairs of initial and recurrent head and neck squamous cell carcinoma tumor cases. Approximately one-third of the recurrent cases showed TP53 status different from that of the initial tumor. Survival after recurrence was associated with the TP53 status of the recurrent tumors, which was prognostically useful.

 The effect of pathological features on radiation prognosis for nasopharyngeal carcinoma was investigated. The prognosis of keratinizing SCC was worse than that of nonkeratinizing SCC, suggesting biological differences. Overexpression of EpCAM was also shown to be a prognostic factor for nonkeratotic SCC.

 Pancreatic cancer: We examined 261 intrahepatic cholangiocarcinoma (iCCA) cases and demonstrated that tertiary lymphoid structure (TLS) was prognostic only in the large-duct type, the tumor microenvironment of TLS-rich iCCA showed a significantly high vein density with a tendency for low immature vessels and an active immune microenvironment, and vein density was prognostic in iCCA patients. Thus, a TLS-rich microenvironment has a high vein density, which represents the antitumor direction of the tumor microenvironment with a favorable patient outcome.

 Trans-organ approach: Fusion genes as drug resistance mechanism were comprehensively studied using CRISPR-modified in vitro models and EGFR mutant lung cancer patient cohort. Through multimodal evaluation of putative fusion oncogenes, we identified that only a minority of them have a role as functional drug resistance, which could be overcome by combination therapies. Our results partially reveal the complex nature of fusion oncogenes as potential drug resistance and highlight approaches that can be taken to determine their functional significance.

 Genomic profiling and molecular pathogenesis of soft tissue and bone tumors

 We established Japan Sarcoma Genome Consortium (JSGC) in 2014 to promote genomic research of bone and soft-tissue tumors. Currently, approximately 30 hospitals and 5 research institutes participate in JSGC and we manage JSGC office under collaboration of the Institute of Medical Science, University of Tokyo.

 We are currently involved with Cancer Whole Genome Analysis Research Project under the AMED Program of Practical Research for Innovative Cancer Control Innovative, based on the Action Plan for Whole Genome Analysis by the MHLW, and conducting a whole genome analysis study of bone and soft tissue tumors.

Education

 We accepted three graduated fellows and trained them in cancer research.

Future Prospects

 With advances in basic research and the spread of cancer genome medicine, fundamental genetic disorders have been discussed in clinical settings. The aim of our research is to use our morphological approach as a means of assigning biological meaning/significance to individual disease and obtaining background molecular features across the organs.

List of papers published in 2022

Journal

1. Eguchi K, Omura G, Shimoi T, Kageyama D, Igaki H, Abe Y, Watanabe T, Aihara Y, Sakai A, Matsumoto Y, Sakai T, Yonemori K, Mori T, Yoshida A, Yoshimoto S. BCOR-CCNB3 sarcoma arising in the pharynx. Auris, nasus, larynx, 50:618-622, 2023

2. Yotsukura M, Muraoka Y, Yoshida Y, Nakagawa K, Shiraishi K, Kohno T, Yatabe Y, Watanabe SI. Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma. Annals of surgical oncology, 30:851-858, 2023

3. Yotsukura M, Muraoka Y, Yoshida Y, Nakagawa K, Shiraishi K, Kohno T, Yatabe Y, Watanabe SI. ASO Visual Abstract: Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma. Annals of surgical oncology, 30:859-860, 2023

4. Sugawara H, Yatabe Y, Watanabe H, Akai H, Abe O, Watanabe SI, Kusumoto M. Radiological precursor lesions of lung squamous cell carcinoma: Early progression patterns and divergent volume doubling time between hilar and peripheral zones. Lung cancer (Amsterdam, Netherlands), 176:31-37, 2023

5. Akamine T, Yotsukura M, Yoshida Y, Nakagawa K, Yatabe Y, Watanabe SI. Feasibility and effectiveness of segmentectomy versus wedge resection for clinical stage I non-small-cell lung cancer. European journal of cardio-thoracic surgery, 63:ezad018, 2023

6. Kadono T, Yamamoto S, Hirose T, Ikeda G, Ohara A, Itoyama M, Yokoyama K, Honma Y, Hashimoto T, Sekine S, Ishiyama K, Oguma J, Daiko H, Kato K. Safety and short-term efficacy of preoperative FOLFOX therapy in patients with resectable esophageal squamous cell carcinoma who are ineligible for cisplatin. Esophagus, 20:109-115, 2023

7. Naka T, Hashimoto T, Cho H, Tanabe N, Yoshida T, Yatabe Y, Yoshikawa T, Abe S, Sekine S. Sporadic and Familial Adenomatous Polyposis-associated Foveolar-type Adenoma of the Stomach. The American journal of surgical pathology, 47:91-101, 2023

8. Seki K, Sakamoto T, Makiguchi ME, Toyoshima N, Takamaru H, Sekiguchi M, Yamada M, Sekine S, Kanemitsu Y, Saito Y. Unexpected adhesive bowel obstruction after endoscopic submucosal dissection of early sigmoid colon cancer. DEN open, 3:e194, 2023

9. Fukushi G, Yamada M, Kakugawa Y, Gotoh M, Tanabe N, Ushiama M, Watanabe T, Yamazaki T, Matsumoto M, Hirata M, Nakajima T, Sugano K, Yoshida T, Matsuda T, Igarashi Y, Saito Y. Genotype-phenotype correlation of small-intestinal polyps on small-bowel capsule endoscopy in familial adenomatous polyposis. Gastrointestinal endoscopy, 97:59-68.e7, 2023

10. Ikeda G, Hijioka S, Nagashio Y, Maruki Y, Ohba A, Hisada Y, Yoshinari M, Harai S, Kitamura H, Koga T, Murashima Y, Maehara K, Okada M, Yamashige D, Okamoto K, Hara H, Hagiwara Y, Agarie D, Takasaki T, Takeshita K, Kawasaki Y, Kondo S, Morizane C, Ueno H, Hiraoka N, Yatabe Y, Saito Y, Iwakiri K, Okusaka T. Fine-needle biopsy with 19G needle is effective in combination with endoscopic ultrasound-guided tissue acquisition for genomic profiling of unresectable pancreatic cancer. Digestive endoscopy, 35:124-133, 2023

11. Fukuta T, Tanaka T, Hashimoto T, Isahaya K, Kubo Y, Yamano Y, Satomi K, Hiraoka N, Shirakawa N, Arakawa A, Ogawa C, Nishimura N, Aoki J, Ito A, Inamoto Y, Kim SW, Fukuda T. Nelarabine-induced myelopathy in patients undergoing allogeneic hematopoietic cell transplantation: a report of three cases. International journal of hematology, 117:933-940, 2023

12. Sumida S, Toki SI, Mori T, Satomi K, Takao S, Nobusawa S, Kakimoto T, Nakagawa S, Ryo E, Matsushita Y, Ichimura K, Nishisho T, Bando Y, Yoshida A. ZFTA::RELA fusion in a distinct liposarcoma morphologically overlapping with chondroid lipoma. Genes, chromosomes & cancer, 62:101-106, 2023

13. Sugino H, Iwata S, Satomi K, Mori T, Nobusawa S, Nagashima T, Matsushita Y, Yatabe Y, Ichimura K, Kawai A, Yoshida A. Keratin-positive fibrotic extraskeletal myxoid chondrosarcoma: a close mimic of myoepithelial tumour. Histopathology, 82:937-945, 2023

14. Kojima N, Mori T, Motoi T, Kobayashi E, Yoshida M, Yatabe Y, Ichikawa H, Kawai A, Yonemori K, Antonescu CR, Yoshida A. Frequent CD30 Expression in an Emerging Group of Mesenchymal Tumors With NTRK, BRAF, RAF1, or RET Fusions. Modern pathology, 36:100083, 2023

15. Okuma HS, Yoshida H, Kobayashi Y, Arakaki M, Mizoguchi C, Inagaki L, Voon PJ, Malik Bin Ismail A, Fen Soo Hoo H, Yusak S, Severino B Imasa M, Nguyen Huy T, Thai Anh T, Kohsaka S, Mano H, Yonemori K, Nakamura K, Yatabe Y. Molecular pathology quality control in Southeast Asia: Results of a multiregional quality assurance study from MASTER KEY Asia. Cancer science, 114:2664-2673, 2023

16. Naka T, Hashimoto T, Yoshida T, Yatabe Y, Sekine S. KLF4 c.A1322C Mutation Is a Consistent and Specific Genetic Feature of Raspberry-like Foveolar-type Adenoma of the Stomach. The American journal of surgical pathology, 47:521-523, 2023

17. Akiyama M, Sakaue S, Takahashi A, Ishigaki K, Hirata M, Matsuda K, Momozawa Y, Okada Y, Ninomiya T, Terao C, Murakami Y, Kubo M, Kamatani Y. Genome-wide association study reveals BET1L associated with survival time in the 137,693 Japanese individuals. Communications biology, 6:143, 2023

18. Kajiwara Y, Oka S, Tanaka S, Nakamura T, Saito S, Fukunaga Y, Takamatsu M, Kawachi H, Hotta K, Ikematsu H, Kojima M, Saito Y, Yamada M, Kanemitsu Y, Sekine S, Nagata S, Yamada K, Kobayashi N, Ishihara S, Saitoh Y, Matsuda K, Togashi K, Komori K, Ishiguro M, Kuwai T, Okuyama T, Ohuchi A, Ohnuma S, Sakamoto K, Sugai T, Katsumata K, Matsushita HO, Yamano HO, Eda H, Uraoka T, Akimoto N, Kobayashi H, Ajioka Y, Sugihara K, Ueno H. Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study. Gastrointestinal endoscopy, 97:1119-1128.e5, 2023

19. Furuya G, Katoh H, Atsumi S, Hashimoto I, Komura D, Hatanaka R, Senga S, Hayashi S, Akita S, Matsumura H, Miura A, Mita H, Nakakido M, Nagatoishi S, Sugiyama A, Suzuki R, Konishi H, Yamamoto A, Abe H, Hiraoka N, Aoki K, Kato Y, Seto Y, Yoshimura C, Miyadera K, Tsumoto K, Ushiku T, Ishikawa S. Nucleic acid-triggered tumoral immunity propagates pH-selective therapeutic antibodies through tumor-driven epitope spreading. Cancer science, 114:321-338, 2023

20. Mitsudomi T, Tan D, Yang JC, Ahn MJ, Batra U, Cho BC, Cornelio G, Lim T, Mok T, Prabhash K, Reungwetwattana T, Ren SX, Singh N, Toyooka S, Wu YL, Yang PC, Yatabe Y. Expert Consensus Recommendations on Biomarker Testing in Metastatic and Nonmetastatic NSCLC in Asia. Journal of thoracic oncology, 18:436-446, 2023

21. Thunnissen E, Beasley MB, Borczuk A, Dacic S, Kerr KM, Lissenberg-Witte B, Minami Y, Nicholson AG, Noguchi M, Sholl L, Tsao MS, Le Quesne J, Roden AC, Chung JH, Yoshida A, Moreira AL, Lantuejoul S, Pelosi G, Poleri C, Hwang D, Jain D, Travis WD, Brambilla E, Chen G, Botling J, Bubendorf L, Mino-Kenudson M, Motoi N, Chou TY, Papotti M, Yatabe Y, Cooper W. Defining Morphologic Features of Invasion in Pulmonary Nonmucinous Adenocarcinoma With Lepidic Growth: A Proposal by the International Association for the Study of Lung Cancer Pathology Committee. Journal of thoracic oncology, 18:447-462, 2023

22. Takahashi T, Nishio M, Nishino K, Yoshiki Y, Shiraiwa N, Emir B, Iadeluca L, Yatabe Y, Nishio K. Real-world study of next-generation sequencing diagnostic biomarker testing for patients with lung cancer in Japan. Cancer science, 114:2524-2533, 2023

23. Ishimoto-Namiki U, Ino Y, Esaki M, Shimada K, Saruta M, Hiraoka N. Novel Insights Into Immunohistochemical Analysis For Acinar Cell Neoplasm of The Pancreas: Carboxypeptidase A2, Carboxypeptidase A1, and Glycoprotein 2. The American journal of surgical pathology, 47:525-534, 2023

24. Tsutani Y, Goldman JW, Dacic S, Yatabe Y, Majem M, Huang X, Chen A, van der Gronde T, He J. Adjuvant Osimertinib vs. Placebo in Completely Resected Stage IA2-IA3 EGFR-Mutated NSCLC: ADAURA2. Clinical lung cancer, 24:376-380, 2023

25. Ohba A, Morizane C, Ueno M, Kobayashi S, Kawamoto Y, Komatsu Y, Ikeda M, Sasaki M, Okano N, Furuse J, Hiraoka N, Yoshida H, Kuchiba A, Sadachi R, Nakamura K, Matsui N, Nakamura Y, Okamoto W, Yoshino T, Okusaka T. Multicenter phase II trial of trastuzumab deruxtecan for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial. Future oncology (London, England), 18:2351-2360, 2022

26. Omura T, Takahashi M, Ohno M, Miyakita Y, Yanagisawa S, Tamura Y, Kikuchi M, Kawauchi D, Nakano T, Hosoya T, Igaki H, Satomi K, Yoshida A, Sunami K, Hirata M, Shimoi T, Sudo K, Okuma HS, Yonemori K, Suzuki H, Ichimura K, Narita Y. Clinical Application of Comprehensive Genomic Profiling Tests for Diffuse Gliomas. Cancers, 14:2454, 2022

27. Satomi K, Yoshida A, Matsushita Y, Sugino H, Fujimoto K, Honda-Kitahara M, Takahashi M, Ohno M, Miyakita Y, Narita Y, Yatabe Y, Shibahara J, Ichimura K. Clinical application of a highly sensitive digital PCR assay to detect a small fraction of IDH1 R132H-mutant alleles in diffuse gliomas. Brain tumor pathology, 39:210-217, 2022

28. Tokura M, Nakayama J, Prieto-Vila M, Shiino S, Yoshida M, Yamamoto T, Watanabe N, Takayama S, Suzuki Y, Okamoto K, Ochiya T, Kohno T, Yatabe Y, Suto A, Yamamoto Y. Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ. Cancer research, 82:3236-3248, 2022

29. Kojima N, Komiyama M, Shinoda Y, Watanabe SI, Yatabe Y, Kawai A, Yoshida A. Liposarcoma With Hibernoma-like Histology: A Clinicopathologic Study of 16 Cases. The American journal of surgical pathology, 46:1319-1328, 2022

30. Higashiyama M, Kobayashi Y, Kashima J, Muraoka Y, Watanabe H, Kusumoto M, Watanabe SI, Yatabe Y. Invasive Mucinous Adenocarcinoma of the Lung With a Mural Nodule-like Lesion. The American journal of surgical pathology, 46:1524-1532, 2022

31. Yotsukura M, Nakagawa K, Takemura C, Yoshida Y, Ito K, Watanabe H, Kusumoto M, Yatabe Y, Watanabe SI. Aggressive histological component in subsolid lung adenocarcinoma: priority for resection without delay. Japanese journal of clinical oncology, 52:1321-1326, 2022

32. Kajiyama A, Ito K, Watanabe H, Mizumura S, Watanabe SI, Yatabe Y, Gomi T, Kusumoto M. Consistency and prognostic value of preoperative staging and postoperative pathological staging using (18)F-FDG PET/MRI in patients with non-small cell lung cancer. Annals of nuclear medicine, 36:1059-1072, 2022

33. Kashima J, Hashimoto T, Yoshida A, Goto Y, Ushiku T, Ohe Y, Watanabe SI, Yatabe Y. Insulinoma-associated-1 (INSM1) expression in thymic squamous cell carcinoma. Virchows Archiv, 481:893-901, 2022

34. Yoshida Y, Saeki N, Yotsukura M, Nakagawa K, Watanabe H, Yatabe Y, Watanabe SI. Visualization of patterns of lymph node metastases in non-small cell lung cancer using network analysis. JTCVS open, 12:410-425, 2022

35. Shinno Y, Yoshida A, Masuda K, Matsumoto Y, Okuma Y, Yoshida T, Goto Y, Horinouchi H, Yamamoto N, Yatabe Y, Ohe Y. Efficacy of Immune Checkpoint Inhibitors in SMARCA4-Deficient Thoracic Tumor. Clinical lung cancer, 23:386-392, 2022

36. Ida H, Koyama T, Mizuno T, Sunami K, Kubo T, Sudo K, Tao K, Hirata M, Yonemori K, Kato K, Okusaka T, Ohe Y, Matsui Y, Yamazaki N, Ogawa C, Kawai A, Narita Y, Esaki M, Yamamoto N. Clinical utility of comprehensive genomic profiling tests for advanced or metastatic solid tumor in clinical practice. Cancer science, 113:4300-4310, 2022

37. Hashimoto T, Takayanagi D, Yonemaru J, Naka T, Nagashima K, Yatabe Y, Shida D, Hamamoto R, Kleeman SO, Leedham SJ, Maughan T, Takashima A, Shiraishi K, Sekine S. Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer. British journal of cancer, 127:1043-1050, 2022

38. Morizane C, Machida N, Honma Y, Okusaka T, Boku N, Kato K, Nomura S, Hiraoka N, Sekine S, Taniguchi H, Okano N, Yamaguchi K, Sato T, Ikeda M, Mizuno N, Ozaka M, Kataoka T, Ueno M, Kitagawa Y, Terashima M, Furuse J. Effectiveness of Etoposide and Cisplatin vs Irinotecan and Cisplatin Therapy for Patients With Advanced Neuroendocrine Carcinoma of the Digestive System: The TOPIC-NEC Phase 3 Randomized Clinical Trial. JAMA oncology, 8:1447-1455, 2022

39. Shimizu Y, Murakami N, Mori T, Takahashi K, Kubo Y, Yoshimoto S, Honma Y, Nakamura S, Okamoto H, Iijima K, Takahashi A, Kaneda T, Kashihara T, Inaba K, Okuma K, Nakayama Y, Igaki H, Itami J. Clinical impact of p16 positivity in nasopharyngeal carcinoma. Laryngoscope investigative otolaryngology, 7:994-1001, 2022

40. Okura K, Esaki M, Nara S, Ban D, Takamoto T, Shimada K, Hiraoka N. Hepatoid carcinoma and related entities of the extrahepatic bile duct: A clinicopathological study of four cases. Pathology international, 72:332-342, 2022

41. Kitamura K, Esaki M, Sone M, Sugawara S, Hiraoka N, Nara S, Ban D, Takamoto T, Mizui T, Shimada K. ASO Author Reflections: Prognostic Impact of Radiological Splenic Artery Involvement in Pancreatic Ductal Adenocarcinoma of the Body and Tail. Annals of surgical oncology, 29:7059-7060, 2022

42. Kitamura K, Esaki M, Sone M, Sugawara S, Hiraoka N, Nara S, Ban D, Takamoto T, Mizui T, Shimada K. Prognostic Impact of Radiological Splenic Artery Involvement in Pancreatic Ductal Adenocarcinoma of the Body and Tail. Annals of surgical oncology, 29:7047-7058, 2022

43. Kitamura K, Esaki M, Sone M, Sugawara S, Hiraoka N, Nara S, Ban D, Takamoto T, Mizui T, Shimada K. ASO Visual Abstract: Prognostic Impact of Radiological Splenic Artery Involvement in Pancreatic Ductal Adenocarcinoma of the Body and Tail. Annals of surgical oncology, 29:7061-7062, 2022

44. Hisada Y, Hijioka S, Ikeda G, Maehara K, Hashimoto T, Kitamura H, Harai S, Yoshinari M, Kawasaki Y, Murashima Y, Koga T, Takeshita K, Maruki Y, Ohba A, Nagashio Y, Kondo S, Morizane C, Ueno H, Saito Y, Yatabe Y, Okusaka T. Proportion of unresectable pancreatic cancer specimens obtained by endoscopic ultrasound-guided tissue acquisition meeting the OncoGuide NCC Oncopanel System analysis suitability criteria: a single-arm, phase II clinical trial. Journal of gastroenterology, 57:990-998, 2022

45. Fukuhara S, Oshikawa-Kumade Y, Kogure Y, Shingaki S, Kariyazono H, Kikukawa Y, Koya J, Saito Y, Tabata M, Yoshifuji K, Mizuno K, Miyagi-Maeshima A, Matsushita H, Sugiyama M, Ogawa C, Inamoto Y, Fukuda T, Sugano M, Yamauchi N, Minami Y, Hirata M, Yoshida T, Kohno T, Kohsaka S, Mano H, Shiraishi Y, Ogawa S, Izutsu K, Kataoka K. Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies. Cancer science, 113:2763-2777, 2022

46. Sone M, Sugawara S, Yatabe Y. Role of Image-Guided Percutaneous Needle Biopsy in the Age of Precision Medicine. Current oncology reports, 24:1035-1044, 2022

47. Imai M, Nakamura Y, Sunami K, Kage H, Komine K, Koyama T, Amano T, Ennishi D, Kanai M, Kenmotsu H, Maeda T, Morita S, Sakai D, Bando H, Makiyama A, Suzuki T, Hirata M, Kohsaka S, Tsuchihara K, Naito Y, Yoshino T. Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors. Cancer science, 113:3646-3656, 2022

48. Hamamoto R, Koyama T, Kouno N, Yasuda T, Yui S, Sudo K, Hirata M, Sunami K, Kubo T, Takasawa K, Takahashi S, Machino H, Kobayashi K, Asada K, Komatsu M, Kaneko S, Yatabe Y, Yamamoto N. Introducing AI to the molecular tumor board: one direction toward the establishment of precision medicine using large-scale cancer clinical and biological information. Experimental hematology & oncology, 11:82, 2022

49. Naito Y, Sunami K, Kage H, Komine K, Amano T, Imai M, Koyama T, Ennishi D, Kanai M, Kenmotsu H, Maeda T, Morita S, Sakai D, Watanabe K, Shirota H, Kinoshita I, Yoshioka M, Mamesaya N, Ito M, Kohsaka S, Saigusa Y, Yamamoto K, Hirata M, Tsuchihara K, Yoshino T. Concordance Between Recommendations From Multidisciplinary Molecular Tumor Boards and Central Consensus for Cancer Treatment in Japan. JAMA network open, 5:e2245081, 2022

50. Kojima N, Arai Y, Satomi K, Kubo T, Matsushita Y, Mori T, Matsushita H, Ushijima T, Yatabe Y, Shibata T, Yonemori K, Ichimura K, Ichikawa H, Kawai A, Yoshida A. Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall. Modern pathology, 35:1439-1448, 2022

51. Saito A, Tanioka M, Hirata M, Watanabe T, Odaka Y, Shimoi T, Sudo K, Noguchi E, Ishikawa M, Yonemori K. Case report: Response to platinum agents and poly (adenosine diphosphate-ribose) polymerase inhibitor in a patient with BRCA1 c.5096G>A (R1699Q) intermediate-risk variant. Cancer treatment and research communications, 32:100587, 2022

52. Takamiya A, Ishibashi Y, Makise N, Hirata M, Ushiku T, Tanaka S, Kobayashi H. Imaging characteristics of NTRK-rearranged spindle cell neoplasm of the soft tissue: A case report. Journal of orthopaedic science, S0949-2658(21)00367-5, 2022

53. Tomida A, Chiyonobu T, Tokuda S, Miyachi M, Murashima K, Hirata M, Nakagawa M, Iehara T, Kuroda J, Takayama K. Pleomorphic rhabdomyosarcoma in a young adult harboring a novel germline MSH2 variant. Human genome variation, 9:8, 2022

54. Momozawa Y, Sasai R, Usui Y, Shiraishi K, Iwasaki Y, Taniyama Y, Parsons MT, Mizukami K, Sekine Y, Hirata M, Kamatani Y, Endo M, Inai C, Takata S, Ito H, Kohno T, Matsuda K, Nakamura S, Sugano K, Yoshida T, Nakagawa H, Matsuo K, Murakami Y, Spurdle AB, Kubo M. Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants. JAMA oncology, 8:871-878, 2022

55. Sekine Y, Iwasaki Y, Aoi T, Endo M, Hirata M, Kamatani Y, Matsuda K, Sugano K, Yoshida T, Murakami Y, Fukui T, Akamatsu S, Ogawa O, Nakagawa H, Numakura K, Narita S, Habuchi T, Momozawa Y. Different risk genes contribute to clear cell and non-clear cell renal cell carcinoma in 1532 Japanese patients and 5996 controls. Human molecular genetics, 31:1962-1969, 2022

56. Usui Y, Iwasaki Y, Matsuo K, Endo M, Kamatani Y, Hirata M, Sugano K, Yoshida T, Matsuda K, Murakami Y, Maeda Y, Nakagawa H, Momozawa Y. Association between germline pathogenic variants in cancer-predisposing genes and lymphoma risk. Cancer science, 113:3972-3979, 2022

57. Mishra A, Malik R, Hachiya T, Jürgenson T, Namba S, Posner DC, Kamanu FK, Koido M, Le Grand Q, Shi M, He Y, Georgakis MK, Caro I, Krebs K, Liaw YC, Vaura FC, Lin K, Winsvold BS, Srinivasasainagendra V, Parodi L, Bae HJ, Chauhan G, Chong MR, Tomppo L, Akinyemi R, Roshchupkin GV, Habib N, Jee YH, Thomassen JQ, Abedi V, Cárcel-Márquez J, Nygaard M, Leonard HL, Yang C, Yonova-Doing E, Knol MJ, Lewis AJ, Judy RL, Ago T, Amouyel P, Armstrong ND, Bakker MK, Bartz TM, Bennett DA, Bis JC, Bordes C, Børte S, Cain A, Ridker PM, Cho K, Chen Z, Cruchaga C, Cole JW, de Jager PL, de Cid R, Endres M, Ferreira LE, Geerlings MI, Gasca NC, Gudnason V, Hata J, He J, Heath AK, Ho YL, Havulinna AS, Hopewell JC, Hyacinth HI, Inouye M, Jacob MA, Jeon CE, Jern C, Kamouchi M, Keene KL, Kitazono T, Kittner SJ, Konuma T, Kumar A, Lacaze P, Launer LJ, Lee KJ, Lepik K, Li J, Li L, Manichaikul A, Markus HS, Marston NA, Meitinger T, Mitchell BD, Montellano FA, Morisaki T, Mosley TH, Nalls MA, Nordestgaard BG, O’Donnell MJ, Okada Y, Onland-Moret NC, Ovbiagele B, Peters A, Psaty BM, Rich SS, Rosand J, Sabatine MS, Sacco RL, Saleheen D, Sandset EC, Salomaa V, Sargurupremraj M, Sasaki M, Satizabal CL, Schmidt CO, Shimizu A, Smith NL, Sloane KL, Sutoh Y, Sun YV, Tanno K, Tiedt S, Tatlisumak T, Torres-Aguila NP, Tiwari HK, Trégouët DA, Trompet S, Tuladhar AM, Tybjærg-Hansen A, van Vugt M, Vibo R, Verma SS, Wiggins KL, Wennberg P, Woo D, Wilson PWF, Xu H, Yang Q, Yoon K, Millwood IY, Gieger C, Ninomiya T, Grabe HJ, Jukema JW, Rissanen IL, Strbian D, Kim YJ, Chen PH, Mayerhofer E, Howson JMM, Irvin MR, Adams H, Wassertheil-Smoller S, Christensen K, Ikram MA, Rundek T, Worrall BB, Lathrop GM, Riaz M, Simonsick EM, Kõrv J, França PHC, Zand R, Prasad K, Frikke-Schmidt R, de Leeuw FE, Liman T, Haeusler KG, Ruigrok YM, Heuschmann PU, Longstreth WT, Jung KJ, Bastarache L, Paré G, Damrauer SM, Chasman DI, Rotter JI, Anderson CD, Zwart JA, Niiranen TJ, Fornage M, Liaw YP, Seshadri S, Fernández-Cadenas I, Walters RG, Ruff CT, Owolabi MO, Huffman JE, Milani L, K. Stroke genetics informs drug discovery and risk prediction across ancestries. Nature, 611:115-123, 2022

58. Tsuda N, Tian Y, Fujimoto M, Kuramoto J, Makiuchi S, Ojima H, Gotoh M, Hiraoka N, Yoshida T, Kanai Y, Arai E. DNA methylation status of the SPHK1 and LTB genes underlies the clinicopathological diversity of non-alcoholic steatohepatitis-related hepatocellular carcinomas. Journal of cancer research and clinical oncology, 2022

59. Sekiguchi M, Hotta K, Takeuchi Y, Tanaka S, Yamamoto H, Shinmura K, Harada K, Uraoka T, Hisabe T, Sano Y, Kondo H, Horimatsu T, Kikuchi H, Kawamura T, Nagata S, Yamamoto K, Tajika M, Tsuji S, Kusaka T, Okuyama Y, Yoshida N, Moriyama T, Hasebe A, So S, Kobara H, Kashida H, Miyanaga R, Kato S, Hayashi Y, Sada M, Fukuzawa M, Kato H, Takayama T, Konishi J, Matsushita HO, Narasaka T, Ohata K, Togashi K, Nakamura H, Moriichi K, Oda Y, Kanda N, Kuwai T, Terai S, Sanomura M, Kitamura S, Miyamoto H, Kiriyama S, Mizuno C, Saito Y, Sekine S, Ito S, Nakahira H, Oka S, Hayashi Y, Yoshimura K, Ishikawa H, Matsuda T. Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY. Journal of gastroenterology, 57:547-558, 2022

60. Sawada J, Hiraoka N, Qi R, Jiang L, Fournier-Goss AE, Yoshida M, Kawashima H, Komatsu M. Molecular Signature of Tumor-Associated High Endothelial Venules That Can Predict Breast Cancer Survival. Cancer immunology research, 10:468-481, 2022

61. Kishikawa S, Hayashi T, Shimizu J, Fuwa B, Nonomura A, Saito T, Yatabe Y, Yao T. Low-grade tracheal adenocarcinoma with ETV6::NTRK3 fusion: unique morphology akin to subsets of sinonasal low-grade non-intestinal-type adenocarcinoma. Virchows Archiv, 481:793-797, 2022

62. Yamamoto M, Kawase Y, Kishi H, Miyoshi Y, Mitsui H, Sekine S. Poromas with YAP1-MAML2 fusions in a poromatosis case. JAAD case reports, 25:39-42, 2022

63. Nicholson AG, Scagliotti G, Tsao MS, Yatabe Y, Travis WD. 2021 WHO Classification of Lung Cancer: A Globally Applicable and Molecular Biomarker-Relevant Classification. Journal of thoracic oncology, 17:e80-e83, 2022

64. Mafficini A, Simbolo M, Shibata T, Hong SM, Pea A, Brosens LA, Cheng L, Antonello D, Sciammarella C, Cantù C, Mattiolo P, Taormina SV, Malleo G, Marchegiani G, Sereni E, Corbo V, Paolino G, Ciaparrone C, Hiraoka N, Pallaoro D, Jansen C, Milella M, Salvia R, Lawlor RT, Adsay V, Scarpa A, Luchini C. Integrative characterization of intraductal tubulopapillary neoplasm (ITPN) of the pancreas and associated invasive adenocarcinoma. Modern pathology, 35:1929-1943, 2022

65. Ahn MJ, Mendoza MJL, Pavlakis N, Kato T, Soo RA, Kim DW, Liam CK, Hsia TC, Lee CK, Reungwetwattana T, Geater S, Chan OSH, Prasongsook N, Solomon BJ, Nguyen TTH, Kozuki T, Yang JC, Wu YL, Mok TSK, Tan DS, Yatabe Y. Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations. Clinical lung cancer, 23:670-685, 2022

66. Mori T. Involvement of the p53-p16/RB pathway control mechanism in early-stage carcinogenesis in head and neck squamous cell carcinoma. Pathology international, 72:577-588, 2022

67. Matsuzaki Y, Naito Y, Miura N, Mori T, Watabe Y, Yoshimoto S, Shibahara T, Takano M, Honda K. RIOK2 Contributes to Cell Growth and Protein Synthesis in Human Oral Squamous Cell Carcinoma. Current oncology (Toronto, Ont.), 30:381-391, 2022

68. To C, Beyett TS, Jang J, Feng WW, Bahcall M, Haikala HM, Shin BH, Heppner DE, Rana JK, Leeper BA, Soroko KM, Poitras MJ, Gokhale PC, Kobayashi Y, Wahid K, Kurppa KJ, Gero TW, Cameron MD, Ogino A, Mushajiang M, Xu C, Zhang Y, Scott DA, Eck MJ, Gray NS, Jänne PA. An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer. Nature cancer, 3:402-417, 2022

69. Yoshida R, Saigi M, Tani T, Springer BF, Shibata H, Kitajima S, Mahadevan NR, Campisi M, Kim W, Kobayashi Y, Thai TC, Haratani K, Yamamoto Y, Sundararaman SK, Knelson EH, Vajdi A, Canadas I, Uppaluri R, Paweletz CP, Miret JJ, Lizotte PH, Gokhale PC, Jänne PA, Barbie DA. MET-Induced CD73 Restrains STING-Mediated Immunogenicity of EGFR-Mutant Lung Cancer. Cancer research, 82:4079-4092, 2022

70. Kobayashi Y, Oxnard GR, Cohen EF, Mahadevan NR, Alessi JV, Hung YP, Bertram AA, Heppner DE, Ribeiro MF, Sacardo KP, Saddi R, Macedo MP, Blasco RB, Li J, Kurppa KJ, Nguyen T, Voligny E, Ananda G, Chiarle R, Katz A, Tolstorukov MY, Sholl LM, Jänne PA. Genomic and biological study of fusion genes as resistance mechanisms to EGFR inhibitors. Nature communications, 13:5614, 2022

71. Liu X, Yamaguchi K, Takane K, Zhu C, Hirata M, Hikiba Y, Maeda S, Furukawa Y, Ikenoue T. Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis. PloS one, 16:e0257090, 2021