Genetic alterations and prognostic factors for primary central nervous system lymphoma treated with R-MPV-A combination immunochemotherapy
Project/Area Number |
26462189
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurosurgery
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Research Institution | Kyorin University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
NAGANE Motoo 杏林大学, 医学部, 教授 (60327468)
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Research Collaborator |
SASAKI Nobuyoshi
LEE Jeunghun
SHIMIZU Saki
SUZUKI Kaori
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 脳腫瘍 / 中枢神経系悪性リンパ腫 / 遺伝子異常 / MGMT / MYD88 / MMSE / 予後因子 / mismatch repair蛋白 / Bcl6 / 全エクソンシークエンス |
Outline of Final Research Achievements |
Primary central nervous system lymphoma (PCNSL) is one of the deadly malignant brain tumors, but exhibits a high response to combination immunochemotherapy with rituximab, methotrexate, procarbazine, vincristine and cytarabine (R-MPV-A). We analyzed 32 patients with newly diagnosed PCNSL composed of diffuse large B cell lymphoma (DLBCL) for potential genetic alterations as well as prognostic factors for progression-free survival (PFS). We found MYD88 mutations in 70% of patients which is much higher than in those with systemic DLBCL, while MGMT promoter was methylated in 60% of cases. Factors associated with longer PFS are age<70 years (p=0.059), single lesion (p=0.010), methylated MGMT promoter (p=0.056), and MMSE score ≧ 24 (p=0.025), but MYD88 mutations did not affect outcome (p=0.186, rather mutated MYD88 patients tended to live longer). These results suggest that methylated MGMT and high baseline MMSE score might predict higher benefit and better outcome with R-MPV-A treatment.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Combined immunochemotherapy, R-MPV-A, with reduced or deferred radiotherapy for PCNSL improves survival with favorable performance and cognitive function (abst #ACTR-23)2016
Author(s)
Nagane M, Keiichi K, Saito K, Sasaki N, Kume S, Yamagishi Y, Shimizu S, Suzuki K, Shiokawa Y
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Journal Title
Neuro-Oncology (suppl)
Volume: 18
Related Report
Peer Reviewed
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[Journal Article] Genomic characterization of primary central nervous system lymphoma2016
Author(s)
Fukumura K, D Kawazu M, Ueno T, Sai E, Soda M, Kojima S, Ueda H, Yasuda T, Yamaguchi H, Lee J, Shishido-Hara Y, Sasaki A, Shirahata M, Mishima K, Ichimura K, Mukasa A, Narita Y, Saito N, Aburatani H, Nishikawa R, Nagane M, Mano H
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Journal Title
Acta Neuropathol
Volume: publish online 12 Jan 2016
Issue: 6
Pages: 865-875
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Combined immunochemotherapy, R-MPV-A, with reduced or deferred radiotherapy for PCNSL improves survival with favorable performance and cognitive function2016
Author(s)
Motoo Nagane, Keiichi Kobayashi, Kuniaki Saito, Nobuyoshi Sasaki, Satoshi Kume, Yuki Yamagishi, Saki Shimizu, Kaori Suzuki, Yoshiaki Shiokawa
Organizer
21th Annual Meeting of the Society for Neuro-Oncology
Place of Presentation
Scottsdale, AZ, U.S.A.
Year and Date
2016-11-18
Related Report
Int'l Joint Research
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[Presentation] Genomic characterization of primary central nervous system lymphoma reveals predominant nonsynonymous somatic mutations of MYD88 and PIM1 genes2016
Author(s)
Nagane M, Fukumura K, Ueno T, Lee J, Shishido-Hara Y, Mishima K, Ichimura K, Mukasa A, Narita Y, Aburatani H, Nishikawa R, Mano H
Organizer
21th International Conference on Brain Tumor Research and Therapy
Place of Presentation
Okinawa, Japan
Year and Date
2016-04-13
Related Report
Int'l Joint Research
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[Presentation] Genomic characterization of primary central nervous system lymphoma reveals predominant nonsynonymous somatic mutations of MYD88 and PIM1 genes2015
Author(s)
Motoo Nagane, Kazutaka Fukumura, Toshihide Ueno, Jeunghun Lee, Yukiko Shishido-Hara, Kazuhiko Mishima, Koichi Ichimura, Akitake Mukasa, Yoshitaka Narita, Hiroyuki Aburatani, Ryo Nishikawa, Hiroyuki Mano
Organizer
20th Scientific Meeting of the Society for Neuro-Oncology
Place of Presentation
San Antonio, TX, USA
Year and Date
2015-11-21
Related Report
Int'l Joint Research
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[Presentation] 中枢神経系原発悪性リンパ腫に対する包括的遺伝子解析2015
Author(s)
Motoo Nagane, Kazutaka Fukumura, Toshihide Ueno, Kazuhiko Mishima, Koichi Ichimura, Akitake Mukasa, Yoshitaka Narita, Hiroyuki Aburatani, Ryo Nishikawa, Hiroyuki Mano
Organizer
第74回日本癌学会学術総会
Place of Presentation
名古屋市
Year and Date
2015-10-10
Related Report
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[Presentation] Whole-exome sequencing analysis of primary central nervous system lymphoma reveals recurrent MYD88 and PIM1 mutations2015
Author(s)
Motoo Nagane, Kazutaka Fukumura, Toshihide Ueno, Jeunghun Lee, Yukiko Shishido-Hara4 Mitsuaki Shirahata, Kazuhiko Mishima, Koichi Ichimura, Akitake Mukasa, Yoshitaka Narita, Ryo Nishikawa, Hiroyuki Mano
Organizer
American Association for Cancer Research (AACR) Annual Meeting 2015
Place of Presentation
Philadelphia, PA, USA
Year and Date
2015-04-21
Related Report
Int'l Joint Research
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