BRAIN and NERVE－神経研究の進歩68巻3号

2016年03月発行

総説

神経膠腫病理診断のベストエビデンス

著者： 増井憲太¹ 小森隆司²

所属機関： ¹東京女子医科大学医学部病理学講座第一 ²東京都立神経病院検査科病理

ページ範囲：P.253 - P.261

文献概要

脳腫瘍分類は形態学に基礎を置く古典的組織分類から分子遺伝学的分類に大きく舵を切ろうとしている。その先駆けとなったのが，大規模ゲノム解析に基づく，神経膠腫の一貫した遺伝学的分類の構築である。本稿では，神経膠腫病理診断における分子遺伝学的知見の現状を確認し，現時点での神経膠腫病理診断におけるベストエビデンスとなりうる，腫瘍型を最も的確に特徴づける主幹遺伝子を同定する試みを紹介する。

参考文献

1)Van den bent MJ: Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician's perspective. Acta Neuropathol 120: 297-304, 2010

2)Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, et al: Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17: 510-522, 2010

3)Weller M, Wick W, Aldape K, Brada M, Berger M, et al: Glioma. Nature Reviews Disease Primers, Article number: 15017, 2015 doi: 10.1038/nrdp.2015.17

4)Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, et al: Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482: 226-231, 2012

5)Cancer Genome Atlas Research Network: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455: 1061-1068, 2008

6)Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, et al: Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17: 98-110, 2010

7)Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds): World Health Organization Classification of Tumours of the Central Nervous System. International Agency for Research on Cancer, Lyon, 2007

8)Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, et al: International Society Of Neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24: 429-435, 2014

9)Reuss DE, Sahm F, Schrimpf D, Wiestler B, Capper D, et al: ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol 129: 133-146, 2015

10)Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, et al: Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372: 2481-2498, 2015

11)Suzuki H, Aoki K, Chiba K, Sato Y, Shiozawa Y, et al: Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 47: 458-468, 2015

12)Arita H, Narita Y, Fukushima S, Tateishi K, Matsushita Y, et al: Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol 126: 267-276, 2013

13)Olar A, Wani KM, Alfaro-Munoz KD, Heathcock LE, van Thuijl HF, et al: IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol 129: 585-596, 2015

14)Sahm F, Reuss D, Koelsche C, Capper D, Schittenhelm J, et al: Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma. Acta Neuropathol 128: 551-559, 2014

15)Hartmann C, Hentschel B, Wick W, Capper D, Felsberg J, et al: Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol 120: 707-718, 2010

16)Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, et al: Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372: 2499-2508, 2015

17)Brennan CW, Verhaak RG, Mckenna A, Campos B, Noushmehr H, et al: The somatic genomic landscape of glioblastoma. Cell 155: 462-477, 2013

18)Kleinschmidt-Demasters BK, Aisner DL, Birks DK, Foreman NK: Epithelioid GBMs show a high percentage of BRAF V600E mutation. Am J Surg Pathol 37: 685-698, 2013

19)Collins VP, Jones DT, Giannini C: Pilocytic astrocytoma: pathology molecular mechanisms and markers. Acta Neuropathol 129: 775-788, 2015

20)Jones DT, Hutter B, Jäger N, Korshunov A, Kool M, et al: Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat Genet 45: 927-932, 2013

21)Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, et al: Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22: 425-437, 2012

22)Bender S, Tang Y, Lindroth AM, Hovestadt V, Jones DT, et al: Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24: 660-672, 2013

23)Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, et al: Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat Med 20: 1394-1396, 2014

24)Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, et al: C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature 506: 451-455, 2014

25)Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, et al: Molecular classification of ependymal tumors across all cns compartments, histopathological grades, and age groups. Cancer Cell 27: 728-743, 2015

26)Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, et al: Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506: 445-450, 2014