Neurological Surgery 脳神経外科50巻1号

2022年01月発行

特集 Precision Medicine—個別化医療を目指した遺伝子診断と新治療の知見 Ⅰ悪性脳腫瘍

小児hemispheric glioma

著者： 中野嘉子¹ 市村幸一² 坂本博昭³⁴

所属機関： ¹東京大学医学部附属病院小児科 ²順天堂大学医学部脳疾患連携分野研究講座 ³大阪市立大学医学部脳神経外科 ⁴大阪市立総合医療センター小児脳神経外科

ページ範囲：P.122 - P.131

Point
・小児hemispheric gliomaにおいては，診断や治療標的として意義のある遺伝子異常が複数存在する．
・特に，BRAF，H3F3A，FGFR1，MYB，MYBL1の異常やNTRK，ALK，ROS1融合遺伝子が重要である．
・分子遺伝学的知見を小児脳腫瘍の予後改善につなげるためには，検査体制や分子標的薬への到達性の向上が求められる．

参考文献

1）Ryall S, et al：Integrated molecular and clinical analysis of 1,000 pediatric low-grade gliomas. Cancer Cell 37：569-583.e5, 2020

2）Mackay A, et al：Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell 32：520-537.e5, 2017

3）Ostrom QT, et al：CBTRUS statistical report：primary brain and other central nervous system tumors diagnosed in the United States in 2013-2017. Neuro Oncol 22（12 Suppl 2）：iv1-iv96, 2020

4）Ryall S, et al：Pediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun 8：30, 2020

5）Pekmezci M, et al：The genetic landscape of ganglioglioma. Acta Neuropathol Commun 6：47, 2018

6）Louis DN, et al：The 2021 WHO Classification of Tumors of the Central Nervous System：a summary. Neuro Oncol 23：1231-1251, 2021

7）Durrant DE, Morrison DK：Targeting the Raf kinases in human cancer：the Raf dimer dilemma. Br J Cancer 118：3-8, 2018

8）Mistry M, et al：BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma. J Clin Oncol 33：1015-1022, 2015

9）Schindler G, et al：Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121：397-405, 2011

10）Lehman NL, et al：Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other cortical-based gliomas of children and young adults. Neuro Oncol 19：31-42, 2017

11）Lassaletta A, et al：Therapeutic and prognostic implications of BRAF V600E in pediatric low-grade gliomas. J Clin Oncol 35：2934-2941, 2017

12）Singh D, et al：Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 337：1231-1235, 2012

13）Slegers RJ, Blumcke I：Low-grade developmental and epilepsy associated brain tumors：a critical update 2020. Acta Neuropathol Commun 8：27, 2020

14）Qaddoumi I, et al：Genetic alterations in uncommon low-grade neuroepithelial tumors：BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology. Acta Neuropathol 131：833-845, 2016

15）Surrey LF, et al：Genomic analysis of dysembryoplastic neuroepithelial tumor spectrum reveals a diversity of molecular alterations dysregulating the MAPK and PI3K/mTOR pathways. J Neuropathol Exp Neurol 78：1100-1111, 2019

16）Lucas CG, et al：Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor. Acta Neuropathol Commun 8：151, 2020

17）Ramsay RG, Gonda TJ：MYB function in normal and cancer cells. Nat Rev Cancer 8：523-534, 2008

18）Cicirò Y, Sala A：MYB oncoproteins：emerging players and potential therapeutic targets in human cancer. Oncogenesis 10：19, 2021

19）Bandopadhayay P, et al：MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat Genet 48：273-282, 2016

20）Tatevossian RG, et al：MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas. Acta Neuropathol 120：731-743, 2010

21）Schwartzentruber J, et al：Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482：226-231, 2012

22）Chen CCL, et al：Histone H3.3G34-mutant interneuron progenitors co-opt PDGFRA for gliomagenesis. Cell 183：1617-1633.e22, 2020

23）Lowe BR, et al：Histone H3 mutations：an updated view of their role in chromatin deregulation and cancer. Cancers（Basel）11：660, 2019

24）Recondo G, et al：Targeting MET dysregulation in cancer. Cancer Discov 10：922-934, 2020

25）Cocco E, et al：NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 15：731-747, 2018

26）Robinson DR, et al：The protein tyrosine kinase family of the human genome. Oncogene 19：5548-5557, 2000

27）Wu G, et al：The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46：444-450, 2014

28）Coccé MC, et al：Identification of ZCCHC8 as fusion partner of ROS1 in a case of congenital glioblastoma multiforme with a t（6;12）（q21;q24.3）. Genes Chromosomes Cancer 55：677-687, 2016

29）International Cancer Genome Consortium PedBrain Tumor Project：Recurrent MET fusion genes represent a drug target in pediatric glioblastoma. Nat Med 22：1314-1320, 2016

30）Deng MY, et al：Molecularly defined diffuse leptomeningeal glioneuronal tumor（DLGNT）comprises two subgroups with distinct clinical and genetic features. Acta Neuropathol 136：239-253, 2018

31）Clarke M, et al：Infant high-grade gliomas comprise multiple subgroups characterized by novel targetable gene fusions and favorable outcomes. Cancer Discov 10：942-963, 2020

32）Tsurubuchi T, et al：Subependymal giant cell astrocytoma harboring a PRRC2B-ALK fusion：a case report. Pediatr Blood Cancer 66：e27995, 2019

33）Kurozumi K, et al：High-grade glioneuronal tumor with an ARHGEF2-NTRK1 fusion gene. Brain Tumor Pathol 36：121-128, 2019

34）Stichel D, et al：Routine RNA sequencing of formalin-fixed paraffin-embedded specimens in neuropathology diagnostics identifies diagnostically and therapeutically relevant gene fusions. Acta Neuropathol 138：827-835, 2019

35）Korshunov A, et al：H3-/IDH-wild type pediatric glioblastoma is comprised of molecularly and prognostically distinct subtypes with associated oncogenic drivers. Acta Neuropathol 134：507-516, 2017

36）Bouffet E, et al：Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol 34：2206-2211, 2016

37）Amayiri N, et al；BMMRD Consortium：High frequency of mismatch repair deficiency among pediatric high grade gliomas in Jordan. Int J Cancer 138：380-385, 2016

38）Shlien A, et al；Biallelic Mismatch Repair Deficiency Consortium：Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers. Nat Genet 47：257-262, 2015

39）Rush S, et al：Brainstem ganglioglioma successfully treated with vemurafenib. J Clin Oncol 31：e159-e160, 2013

40）Lassaletta A, et al：Profound clinical and radiological response to BRAF inhibition in a 2-month-old diencephalic child with hypothalamic/chiasmatic glioma. Pediatr Blood Cancer 63：2038-2041, 2016

41）Fangusaro J, et al：Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma：a multicentre, phase 2 trial. Lancet Oncol 20：1011-1022, 2019

42）Hargrave DR, et al：Efficacy and safety of dabrafenib in pediatric patients with BRAF V600 mutation-positive relapsed or refractory low-grade glioma：results from a phase Ⅰ/Ⅱa study. Clin Cancer Res 25：7303-7311, 2019

43）Bernstein A, et al：Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors：a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity. J Neurosurg 133：1704-1709, 2020（Online Publication Date 1 Nov 2019）

44）Robert C, et al：Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med 372：30-39, 2015

45）Laetsch TW, et al：Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions：phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 19：705-714, 2018

46）Desai AV, et al：Updated entrectinib data in children and adolescents with recurrent or refractory solid tumors, including primary CNS tumors. J Clin Oncol 38（15_suppl）：107, 2020

47）Perreault S, et al：RARE-07. Efficacy and safety of larotrectinib in pediatric patients With tropomyosin receptor kinase（TRK）fusion-positive primary central nervous system（CNS）tumors. Neuro Oncol 23（Suppl 1）：i42, 2021

48）Schram AM, et al：Fusions in solid tumours：diagnostic strategies, targeted therapy, and acquired resistance. Nat Rev Clin Oncol 14：735-748, 2017

49）Perreault S, et al：Canadian consensus for biomarker testing and treatment of TRK fusion cancer in pediatric patients. Curr Oncol 28：346-366, 2021

50）Bagchi A, et al：Lorlatinib in a child with ALK-fusion-positive high-grade glioma. N Engl J Med 385：761-763, 2021

51）Guerrini-Rousseau L, et al：Constitutional mismatch repair deficiency-associated brain tumors：report from the European C4CMMRD consortium. Neurooncol Adv 1：vdz033, 2019

52）市川　仁：小児固形腫瘍のゲノムの展望．小児診療 83：505-510, 2020

53）中野嘉子，熊本忠史：小児期に発症する遺伝性腫瘍について．日小児血がん会誌 58：124-131, 2021

54）Bennett J, et al：Canadian pediatric neuro-oncology standards of practice. Front Oncol 10：593192, 2020

55）Hwang TJ, et al：Pediatric trials for cancer therapies with targets potentially relevant to pediatric cancers. J Natl Cancer Inst 112：224-228, 2020

56）Barry E, et al：Navigating the regulatory landscape to develop pediatric oncology drugs：expert opinion recommendations. Paediatr Drugs 23：381-394, 2021