ゲノム病理ユニット
当ユニットは、分子病理学的方法により病院、研究所等の研究を支援することで、がん研究を多面的な視点から活性化し、研究成果をがん医療の進歩に貢献することを目的として令和2年4月に発足した部署です。本ユニットは病院・研究所等の各診療科・部門との共同研究を積極的に進めて行きますので、研究テーマをお持ちの方はお気軽にご相談ください。
スタッフ
| 本間 圭一郎 | ユニット長（兼任） |
| 久木田 洋児 | チームリーダー |
研究テーマ
希少がん診断のための免疫染色、FISHならびに次世代シーケンサーによる遺伝子検査を組み合わせた診断パネルの構築
希少がんは希少であるがゆえに病理診断が難しいがんです。しかし、病理診断の正確さがその後の治療を大きく左右し、また中には急激な経過をたどる疾患があるため診断の迅速性も求められます。
ゲノム病理ユニットでは、特に診断が困難な希少がんの中でもさらに稀ながんを選び、診断過程をパネル化することにより迅速かつ正確な病理診断の可能性を探ります。方法として免疫染色パネルによる診断を基本とし、必要に応じてFISHならびに次世代シーケンサーを用いた診断方法の確立を目指します。
論文
1. Nakamura H, Kukita Y, Yoshida K,Takenaka S, Yagi T. Aggressive Undifferentiated Small Round Cell Sarcoma of the Thorax Showing TOP2B::UBA3 Fusion. Histopathology, 2024, in press.
2. Goto K, Kiniwa Y, Kukita Y, Ohe S, Hiraki T, Hishima T, Takai T, Honma K. Recurrent GATA3 P409Afs*99 frameshift extension mutations in sweat-gland carcinoma with neuroendocrine differentiation. American Journal of Surgical Pathology, 2024, in press. doi: 10.1097/PAS.0000000000002195.
3. Masuda M, Iida K, Iwabuchi S, Tanaka M, Kubota S, Uematsu H, Onuma K, Kukita Y, Kato K, Kamiura S, Nakajima A, Coppo R, Kanda M, Yoshino K, Ueda Y, Morii E, Kimura T, Kondo J, Okada-Hatakeyama M, Hashimoto S, Inoue M. Clonal origin and lineage ambiguity in mixed neuroendocrine carcinoma of the uterine cervix. The American Journal of Pathology, 2024, 194:415-429. doi.org/10.1016/j.ajpath.2023.11.013.
4. Yoshida K, Kukita Y, Nakamura H, Wakamatsu T, Honma K, Yagi T. A case of spindle cell rhabdomyosarcoma with a ZFP64::NCOA3 fusion. Genes Chromosomes & Cancer, 2024, 63:e23212. doi.org/10.1002/gcc.23212.
5. Kukita Y, Kunimasa K, Akazawa T, Mizote Y, Tahara H. A method for extending target regions of genomic profiling by combining a custom probe pool with a commercial targeted panel. The Journal of Applied Laboratory Medicine, 2023, 8:1065-1073. doi.10.1093/jalm/jfad069.
6. Nakamura H, Kukita Y, Wakamatsu T, Takenaka S, Yoshida K, Yagi T. KMT2A-Rearranged Sarcoma with Unusual Fusions: CBX6::KMT2A::PYGO1. Virchows Archiv, 2023, 483:891-897. doi: 10.1007/s00428-023-03639-x
7. Motoi T, Hirata M, Kukita Y, Satomi K, Tamura H, Adachi S, Matsushita Y, Horiguchi S, Hishima T, Ikegami M, Okuma T, Tao K, Arakawa A, Ogawa C, Matsuda K, Ichimura K, Nakamura H, Mori T, Yoshida A. KDM2B-rearranged soft-tissue sarcomas expand the concept of BCOR-associated sarcoma. Modern Pathology, 2023, 36:100317. doi: 10.1016/j.modpat.2023.100317.
8. Yagi T, Nakamura H, Kukita Y, Wakamatsu T, Tamiya H, Nakai S, Watanabe M, Kakunaga S, Takami H, Suzuki R, Takenaka S Hashii Y. Secondary leiomyosarcoma of the nasal cavity in a treated patient with possible hereditary retinoblastoma with germline reciprocal translocation of RB1 and DMXL1 and somatic TP53 mutation: A case report. Molecular and Clinical Oncology, 2023, 19:65. doi.org/10.3892/mco.2023.2661.
9. Goto K, Yoshikawa S, Takai T, Tachibana K, Honma K, Isei T, Kukita Y, Oishi T. Clinicopathologic and genetic characterization of invasive melanoma with BRAF V600K mutation: a study of 16 cases. Journal of Cutaneous Pathology, 2023, 50:739-747. doi.org/10.1111/cup.14470.
10. Kato K, Okami J, Nakamura H, Honma K, Sato Y, Nakamura S, Kukita Y, Nakatsuka S-i, Higashiyama M. Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics. Diagnostics, 2023, 13:1476. doi.org/10.3390/diagnostics13081476
11. Nagayasu MA, Tanaka H, Nogami K, Kukita Y, Nakamura H, Motoi T, Manabe T, Kataoka H. Cutaneous syncytial myoepithelioma with folliculocentric growth and EWSR1 gene rearrangement: A case report. Journal of Cutaneous Pathology, 2023, 50:400-404. doi.org/10.1111/cup.14419.
12. Yamai T, Ikezawa K, Sugimoto, N, Urabe M, Kai Y, Takada R, Nakabori T, Uehara H, Kawamura T, Kunimasa K, Yamamoto S, Wakamatsu T, Hayashi T, Kukita Y, Fujisawa F, Inoue T, Yamaguchi Y, Yamasaki T, Honma K, Ohkawa K. Utility of Comprehensive Genomic Profiling Tests for Patients with Incurable Pancreatic Cancer in Clinical Practice. Cancers, 2023, 15:970. doi.org/10.3390/cancers15030970.
13. Yoshida K, Kukita Y, Nakamura H, Nakai S, Homma K, Yagi T. A case of spindle cell rhabdomyosarcoma with an EP300::VGLL3 fusion. Genes Chromosomes & Cancer, 2023, 62:184-186. doi.org/10.1002/gcc.23113.
14. Kunimasa K, Hirotsu Y, Amemiya K, Honma K, Nakamura H, Nishino K, Omata M. Genetic dissection of intratumor heterogeneity of PD-L1 expression in EGFR-mutated lung adenocarcinoma. Thoracic Cancer, 2023, 14:2210-2215. doi: 10.1111/1759-7714.15038.
15. Nishikawa T, Inoue T, Otsuka T, Kuno I, Kukita Y, Nakamura H, Ikeda Y, Yasui T, Shioyama W, Oka T, Honma K, Hatakeyama K, Miyata H, Isei T, Ishihara R, Kumagai T, Nishimura K, Fujita M. Prevalence and characteristics of immune checkpoint inhibitor-related myocardial damage: A prospective observational study. PLoS One, 2022, 17:e0275865. doi.org/10.1371/journal.pone.0275865.
16. Kunimasa K, Sugimoto N, Kawamura T, Yamasaki T, Honma K, Nagata S, Kukita Y, Fujisawa F, Inoue T, Yamaguchi Y, Kitasaka M, Wakamatsu T, Yamai T, Yamamoto S, Hayashi T, Inoue T, Tamiya M, Imamura F, Nishimura K, Nishino K. Clinical application of comprehensive genomic profiling panel to thoracic malignancies: A single-center retrospective study. Thoracic Cancer, 2022, 13:2970–2977. doi: 10.1111/1759-7714.14643.
17. Nakamura H, Kukita Y, Tamiya H, Takenaka S, Yagi T. A novel EWSR1-HOXB13 rearrangement in a fibroblastic tumor from the abdomen of a young woman. Virchows Archiv, 2022, 481:499-503. doi: 10.1007/s00428-022-03282-y.
18. Tachibana K, Goto K, Kukita Y, Honma K, Isei T, Sugihara S, Taniguchi K, Yamasaki O. BRAF immunoexpression can be intralesionally heterogeneous but BRAF V600E mutation status Is intralesionally homogeneous and interlesionally concordant in melanoma: A study of 140 lesions from 98 patients. The American Journal of Dermatopathology, 2022, 44:478-487. doi: 10.1097/DAD.0000000000002146.
19. Goto K, Yoshikawa S, Kiyohara Y, Kukita Y, Miura K, Oishi T. Co-existence of BRAF V600E-mutated malignant melanoma and BRAF V600E-mutated Langerhans cell histiocytosis: A case report. Journal of Cutaneous Pathology, 2022, 49:393-398. doi: 10.1111/cup.14171.
20. Kukita Y, Nakamura H, Takenaka S, Yagi T. Fragmentation Coefficient of RNA in Formalin-fixed Paraffin-embedded Samples Stored for Long-term at Room Temperature. The Journal of Applied Laboratory Medicine, 2022, 7:619-622. doi: 10.1093/jalm/jfab166.
21. Goto K, Kukita Y, Honma K, Ohike N, Komori T, Ishida Y, Ishikawa M, Nakatsuka T, Fumita S, Nakagawa K, Okabayashi A, Iwahashi Y, Tanino T, Kikuchi K, Kawahara Y, Hishima T, Uehara J, Oishi T, Isei T. Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): a clinicopathologic study of 13 cases with genetic analysis. Modern Pathology, 2022, 35:33-43. doi: 10.1038/s41379-021-00921-8.
22. Kunimasa K, Hirotsu Y, Amemiya K, Nakamura H, Nishino K, Honma K, Okami J, Omata M, Kumagai T. TP53 Loss of Heterozygosity Induces De Novo SCLC Formation in EGFR-Mutated Lung Adenocarcinoma: A Case Report. JTO Clinical and Research Reports, 2022, 3:100305. doi: 10.1016/j.jtocrr.2022.100305.
23. Nakamura H, Koyanagi Y, Kitamura M, Kukita Y. Primary Epithelioid Rhabdomyosarcoma of the Liver: Case Report of an Unusual Histological Variant. International Journal of Surgical Pathology, 2021, 30:331-334. doi: 10.1177/10668969211049832.
24. Kunimasa K, Okami J, Takenaka S, Honma K, Kukita Y, Nagata S, Kawamura T, Inoue T, Tamiya M, Kuhara H, Nishino K, Tahara H, Kumagai T. Conversion surgery for advanced thoracic SMARCA4-deficient undifferentiated tumor with atezolizumab in combination with bevacizumab, paclitaxel and carboplatin treatment ; A case report. JTO Clinical and Research Reports, 2021, 2:100235. doi.org/10.1016/j.jtocrr.2021.100235.
25. Goto K, Kukita Y, Honma K, Ogawa K, Nishida H, Takai T, Oishi T, Hishima T, Tanaka M, Isei T. Signet-ring cell/histiocytoid carcinoma of the axilla: a clinicopathological and genetic analysis of 11 cases, review of the literature, and comparison with potentially related tumours. Histopathology, 2021, 79:926-939. doi: 10.1111/his.14436.
26. Nakamura H, Kukita Y, Kunimasa K, Kittaka N, Kusama H, Nakayama T, Tamaki Y, Sugiura R, Yasuda H, Hashimoto M, Yamamoto T, Imamura F, Nakatsuka SI. α-Methylacyl-CoA racemase: a useful immunohistochemical marker of breast carcinoma with apocrine differentiation. Human Pathology, 2021, 116:39-48. doi: 10.1016/j.humpath.2021.07.005.
27. Nakamura H, Kukita Y, Takenaka S, Yagi T. Malignant epithelioid soft-tissue tumour with NRID1-MAML1 fusion. Histopathology, 2021, 79:1112-1114. doi: 10.1111/his.14455.
28. Kunimasa K, Hirotsu Y, Kukita Y, Ueda Y, Sato Y, Kimura M, Otsuka T, Hamamoto Y, Tamiya M, Inoue T, Kawamura T, Nishino K, Amemiya K, Goto T, Mochizuki H, Honma K, Omata M, Kumagai T. EML4-ALK fusion variant.3 and co-occurrent PIK3CA E542K mutation exhibiting primary resistance to three generations of ALK inhibitors. Cancer Genetics, 2021, 256-257:131-135. doi: 10.1016/j.cancergen.2021.05.010.
29. Kawachi H, Kunimasa K, Kukita Y, Nakamura H, Honma K, Kawamura T, Inoue T, Tamiya M, Kuhara H, Nishino K, Mizote Y, Akazawa T, Tahara H, Kumagai T. Atezolizumab with bevacizumab, paclitaxel and carboplatin was effective for patients with SMARCA4-deficient thoracic sarcoma. Immunotherapy, 2021, 13:799-806. . doi: 10.2217/imt-2020-0311.
30. Hamamoto Y, Kukita Y, Kitamura M, Kurashige M, Masaie H, Fuji S, Ishikawa J, Honma K, Wakasa T, Hanamoto H, Hirokawa M, Suzuki A, Morii E, Nakatsuka SI. Bcl-2-negative IGH-BCL2 translocation-negative follicular lymphoma of the thyroid differs genetically and epigenetically from Bcl-2-positive IGH-BCL2 translocation-positive follicular lymphoma. Histopathology, 2021, 79:521-532. doi: 10.1111/his.14378.
31. Kunimasa K, Nishino K, Kukita Y, Matsumoto S, Kawachi H, Kawamura T, Inoue T, Tamiya M, Honma K, Sugimoto N, Yamasaki T, Imamura F, Goto K, Kumagai T. Late recurrence of lung adenocarcinoma harboring EGFR exon 20 Insertion (A763_Y764insFQEA) mutation successfully treated with osimertinib. Cancer Genetics, 2021, 256-257:57-61. doi: org/10.1016/j.cancergen.2021.04.001.
32. Kimura T, Higashiyama M, Honma K, Nakamura H, Maniwa T, Okami J. Long-term survival in thymic carcinoma with postoperative pleural dissemination. Surgical Case Reports, 2021, 7:171. doi: 10.1186/s40792-021-01255-y.
33. Fujisawa F, Kunimasa K, Kano-Fujiwara R, Sato Y, Kusama H, Nishio M, Matsui S, Yoshinami T, Kittaka N, Nakamura H, Nagata S, Honma K, Yagi T, Nakayama T, Tamaki Y, Imamura F. STK11 loss drives rapid progression in a breast cancer patient resulting in pulmonary tumor thrombotic microangiopathy. Breast Cancer, 2021, 28:765-771. doi: 10.1007/s12282-020-01200-1.
34. Kimura T, Nakamura H, Omura A, Ike A, Hiroshima T, Maniwa T, Honma K, Higashiyama M, Okami J. Novel imprint cytological classification is correlated with tumor spread through air spaces in lung adenocarcinoma. Lung Cancer, 2020, 148:62-68. doi: 10.1016/j.lungcan.2020.08.005.
