2017 Fiscal Year Research-status Report
発生部位による microsatellite stable型大腸癌の分子解析
Project/Area Number |
17K08700
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Research Institution | Iwate Medical University |
Principal Investigator |
菅井 有 岩手医科大学, 医学部, 教授 (20187628)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 大腸癌 / Microsatellite stable / Copy Number alteration / TP53 / KRAS / BRAF / 腫瘍発生 / 発生部位 |
Outline of Annual Research Achievements |
本研究では大腸癌 92 例を用い、microsatellite stable (MSS) 型を呈した 71 例(左側癌 56 例,右側癌 15 例)について変異解析(TP53、KRAS、BRAF、PI3K)、DNA メチル化解析(高メチル化状態、中メチル化状態、低メチル化状態に分類)、CNA(Copy Number Alteration) (gain, lossに大別し後者はLOHとcopy neutral LOHに分類))解析を行い、発生部位による分子異常の特徴について検討した。加えてCNAについてはCNAを示した各染色体上のDNAの長さの総和についても算出した。変異解析では右側 MSS 型癌に KRAS 変異の頻度が高く、左側 MSS 型癌に TP53 変異が多かった。DNA メチル化解析では両群間とも中から低メチル化状態が多かった。CNA 解析では左側 MSS 型癌では、CN gain が多数の染色体に高頻度に生じ、CN gain の 長さが有意に長かった。また、左側 MSS 型癌では 9q、10q、12q の CN gain が有意に高く、右側 MSS 型癌では 3p、16p の CN LOHが有意に高かった。MSS 型癌では発生部位により異なる分子異常を認め、両群間の腫瘍発生の機序が異なることが示唆された。
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Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
以下のように解析結果が得られた。右側 MSS 型癌に KRAS 変異の頻度が高く、左側 MSS 型癌に TP53 変異が多かった。DNA メチル化解析では両群間とも中から低メチル化状態が多かった。CNA 解析では左側 MSS 型癌では、CN gain が多数の染色体に高頻度に生じ、CN gain の 長さが有意に長かった。また、左側 MSS 型癌では 9q、10q、12q の CN gain が有意に高く、右側 MSS 型癌では 3p、16p の CN LOHが有意に高かった。研究成果については”Takahashi Y, Sugai T, Habano W, Ishida K, Eizuka M, Otsuka K, Sasaki A, Takayuki Matsumoto, Morikawa T, Unno M, Suzuki H. Molecular differences in the microsatellite stable phenotype between left-sided and right-sided colorectal cancer. Int J Cancer. 2016;139:2493-501.”に受理された。
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Strategy for Future Research Activity |
MSS型大腸癌(大腸癌の90%)の発生部位により差異を明らかにすることにより、両者の予後の差、化学療法の差などを明らかにする。大腸癌における発生部位による分子レベルの差異を明らかにすることは大腸癌のprecision medicineにも貢献することが期待される。今後の研究テーマとしては発生部位による分子異常のキー遺伝子の異常を明らかにする。今回の検討では左側型MSS型癌で12q14.1-14.2に位置するCDK4/6のコピー数増加がみられた。現在CDK4/6の発現異常について免疫組織化学的に解析している。一部の症例でCDK4/6の過剰発現がみられており、左側癌のターゲット遺伝子として有用性が期待される。今後さらに症例数を増やして検討を行う。
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Causes of Carryover |
(理由) 予定通り進んだが、誤差として生じた。 (使用計画) 平成30年度はこの残高を含め、大腸癌の変異解析・DNAメチル化解析・CNA解析用試薬の購入に使用する。
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Research Products
(71 results)
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[Journal Article] Molecular profiling and genome-wide analysis based on somatic copy number alterations in advanced colorectal cancers.2018
Author(s)
Sugai T, Takahashi Y, Eizuka M, Sugimoto R, Fujita Y, Habano W, Otsuka K, Sasaki A, Yamamoto E, Matsumoto T, Suzuki H.
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Journal Title
Mol Carcinog.
Volume: 57
Pages: 451-461
DOI
Peer Reviewed / Open Access
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[Journal Article] Molecular profiling and comprehensive genome-wide analysis of somatic copy number alterations in gastric intramucosal neoplasias based on microsatellite status.2018
Author(s)
Sugai T, Eizuka M, Arakawa N, Osakabe M, Habano W, Fujita Y, Yamamoto E, Yamano H, Endoh M, Matsumoto T, Suzuki H.
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Journal Title
Gastric Cancer.
Volume: 21
Pages: 765-775
DOI
Peer Reviewed / Open Access
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[Journal Article] Correlation between CT morphologic appearance and histologic findings in colorectal liver metastasis after preoperative chemotherapy.2018
Author(s)
Ishida K, Tamura A, Kato K, Uesugi N, Osakabe M, Eizuka M, Hasegawa Y, Nitta H, Otsuka K, Sasaki A, Ehara S, Sugai T.
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Journal Title
Abdom Radiol (NY).
Volume: 43
Pages: 2991-3000
DOI
Peer Reviewed / Open Access
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[Journal Article] Pentalogy of Cantrell in a monozygotic twin with a giant omphalocele firmly attached to the amniotic membrane: successful prenatal diagnosis and cesarean delivery.2018
Author(s)
Kanasugi T, Kikuchi A, Uesugi N, Fukagawa D, Chida H, Sasaki Y, Haba G, Isurugi C, Oyama R, Sugai T, Sugiyama T.
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Journal Title
Congenit Anom (Kyoto).
Volume: 58
Pages: 73-74
DOI
Peer Reviewed / Open Access
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[Journal Article] Clinicopathological Features and Magnifying Chromoendoscopic Findings of Non-Ampullary Duodenal Epithelial Tumors.2018
Author(s)
Toya Y, Endo M, Akasaka R, Urushikubo J, Gonai T, Asakura K, Yanai S, Kawasaki K, Eizuka M, Uesugi N, Nakamura S, Sugai T, Matsumoto T.
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Journal Title
Digestion.
Volume: 97
Pages: 219-227
DOI
Peer Reviewed
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[Journal Article] Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.2018
Author(s)
Aoki H, Yamamoto E, Yamano HO, Sugai T, Kimura T, Tanaka Y, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Nakaoka M, Yoshida Y, Harada T, Sudo G, Eizuka M, Yorozu A, Kitajima H, Niinuma T, Kai M, Nojima M, Suzuki H, Nakase H.
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Journal Title
Dig Dis Sc.i
Volume: 63
Pages: 1920-1928
DOI
Peer Reviewed
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[Journal Article] Genetic differences stratified by PCR-based microsatellite analysis in gastric intramucosal neoplasia.2017
Author(s)
Sugai T, Sugimoto R, Habano W, Endoh M, Eizuka M, Tsuchida K, Yamamoto E, Kawasaki K, Yanai S, Matsumoto T, Suzuki H.
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Journal Title
Gastric Cancer.
Volume: 20
Pages: 286-296
DOI
Peer Reviewed / Open Access
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[Journal Article] Analysis of molecular alterations in laterally spreading tumors of the colorectum.2017
Author(s)
Sugai T, Habano W, Takagi R, Yamano H, Eizuka M, Arakawa N, Takahashi Y, Yamamoto E, Kawasaki K, Yanai S, Ishida K, Suzuki H, Matsumoto T.
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Journal Title
J Gastroenterol.
Volume: 52
Pages: 715-723
DOI
Peer Reviewed / Open Access
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[Journal Article] A case of intravascular papillary endothelial hyperplasia of the stomach leading to a novel hypothesis for the pathogenesis.2017
Author(s)
Eizuka M, Tsuchida K, Sugimoto R, Ishida K, Uesugi N, Yanai S, Akasaka R, Toya Y, Kawasaki K, Nakamura S, Matsumoto T, Sugai T.
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Journal Title
Histopathology.
Volume: 70
Pages: 672-674
DOI
Peer Reviewed / Open Access
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[Journal Article] Clinicopathological and molecular stability and methylation analyses of gastric papillary adenocarcinoma.2017
Author(s)
Uesugi N, Sugai T, Sugimoto R, Eizuka M, Fujita Y, Sato A, Osakabe M, Ishida K, Koeda K, Sasaki A, Matsumoto T.
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Journal Title
Pathology.
Volume: 49
Pages: 596-603
DOI
Peer Reviewed
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[Journal Article] Tumor budding at the invasive front of colorectal cancer may not be associated with the epithelial-mesenchymal transition.2017
Author(s)
Yamada N, Sugai T, Eizuka M, Tsuchida K, Sugimoto R, Mue Y, Suzuki M, Osakabe M, Uesugi N, Ishida K, Otsuka K, Matsumoto T.
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Journal Title
Hum Pathol.
Volume: 60
Pages: 151-159
DOI
Peer Reviewed / Open Access
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[Journal Article] Case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway.2017
Author(s)
Uesugi N, Sugimoto R, Eizuka M, Fujita Y, Osakabe M, Koeda K, Kosaka T, Yanai S, Ishida K, Sasaki A, Matsumoto T, Sugai T.
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Journal Title
World J Clin Cases.
Volume: 5
Pages: 397-402
DOI
Peer Reviewed / Open Access
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[Journal Article] Genome-wide analysis of DNA copy number alterations in early and advanced gastric cancers.2017
Author(s)
Arakawa N, Sugai T, Habano W, Eizuka M, Sugimoto R, Akasaka R, Toya Y, Yamamoto E, Koeda K, Sasaki A, Matsumoto T, Suzuki H.
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Journal Title
Mol Carcinog.
Volume: 56
Pages: 527-537
DOI
Peer Reviewed / Open Access
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[Journal Article] Inhibition of Aurora Kinase A Synergistically Enhances Cytotoxicity in Ovarian Clear Cell Carcinoma Cell Lines Induced by Cisplatin: A Potential Treatment Strategy.2017
Author(s)
Chiba Y, Sato S, Itamochi H, Yoshino N, Fukagawa D, Kawamura H, Suga Y, Kojima-Chiba A, Muraki Y, Sugai T, Sugiyama T.
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Journal Title
Int J Gynecol Cancer.
Volume: 27
Pages: 1666-1674
DOI
Peer Reviewed
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[Journal Article] Epigenetic silencing of diacylglycerol kinase gamma in colorectal cancer.2017
Author(s)
Kai M, Yamamoto E, Sato A, Yamano HO, Niinuma T, Kitajima H, Harada T, Aoki H, Maruyama R, Toyota M, Hatahira T, Nakase H, Sugai T, Yamashita T, Toyota M, Suzuki H.
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Journal Title
Mol Carcinog.
Volume: 56
Pages: 1743-1752
DOI
Peer Reviewed / Open Access
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[Journal Article] Endoscopic and Molecular Characterization of Colorectal Sessile Serrated Adenoma/polyps with Cytological Dysplasia.2017
Author(s)
Tanaka Y, Yamano HO, Yamamoto E, Matushita HO, Aoki H, Yoshikawa K, Takagi R, Harada E, Nakaoka M, Yoshida Y, Eizuka M, Sugai T, Suzuki H, Nakase H.
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Journal Title
Gastrointest Endosc.
Volume: 86
Pages: 1131-1138
DOI
Peer Reviewed
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[Journal Article] Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination for castration resistant prostate cancer.2017
Author(s)
Obara W, Sato F, Takeda K, Kato R, Kato Y, Kanehira M, Takata R, Mimata H, Sugai T, Nakamura Y, Fujioka T.
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Journal Title
Cancer Sci.
Volume: 108
Pages: 1452-1457
DOI
Peer Reviewed / Open Access
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[Journal Article] Downregulation of miR-186 is associated with metastatic recurrence of gastrointestinal stromal tumors.2017
Author(s)
Niinuma T, Kai M, Kitajima H, Yamamoto E, Harada T, Maruyama R, Nobuoka T, Nishida T, Kanda T, Hasegawa T, Tokino T, Sugai T, Shinomura Y, Nakase H, Suzuki H.
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Journal Title
Oncol Lett.
Volume: 14
Pages: 5703-5710
DOI
Peer Reviewed / Open Access
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[Journal Article] Association between white opaque substance under magnifying colonoscopy and lipid droplets in colorectal epithelial neoplasms.2017
Author(s)
Kawasaki K, Eizuka M, Nakamura S, Endo M, Yanai S, Akasaka R, Toya Y, Fujita Y, Uesugi N, Ishida K, Sugai T, Matsumoto T.
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Journal Title
World J Gastroenterol.
Volume: 23
Pages: 8367-8375
DOI
Peer Reviewed / Open Access
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[Journal Article] Sporadic breast metastasis derived from renal cell carcinoma: A case report.2017
Author(s)
Ikarashi D, Ishida K, Kashiwaba M, Kato Y, Shiomi E, Takayama M, Komatsu H, Takata R, Ohmori S, Sugai T, Obara W.
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Journal Title
Urol Case Rep.
Volume: 16
Pages: 126-128
DOI
Peer Reviewed / Open Access
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[Journal Article] Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer.2017
Author(s)
Aoki H, Yamamoto E, Takasawa A, Niinuma T, Yamano HO, Harada T, Matsushita HO, Yoshikawa K, Takagi R, Harada E, Tanaka Y, Yoshida Y, Aoyama T, Eizuka M, Yorozu A, Kitajima H, Kai M, Sawada N, Sugai T, Nakase H, Suzuki H.
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Journal Title
Oncotarget.
Volume: 9
Pages: 4707-4721
DOI
Peer Reviewed / Open Access
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