TY - JOUR
T1 - Diffuse Midline Gliomas with Histone H3-K27M Mutation
T2 - A Series of 47 Cases Assessing the Spectrum of Morphologic Variation and Associated Genetic Alterations
AU - Solomon, David A.
AU - Wood, Matthew D.
AU - Tihan, Tarik
AU - Bollen, Andrew W.
AU - Gupta, Nalin
AU - Phillips, Joanna J.J.
AU - Perry, Arie
N1 - Publisher Copyright:
© 2015 International Society of Neuropathology
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Somatic mutations of the H3F3A and HIST1H3B genes encoding the histone H3 variants, H3.3 and H3.1, were recently identified in high-grade gliomas arising in the thalamus, pons and spinal cord of children and young adults. However, the complete range of patients and locations in which these tumors arise, as well as the morphologic spectrum and associated genetic alterations remain undefined. Here, we describe a series of 47 diffuse midline gliomas with histone H3-K27M mutation. The 25 male and 22 female patients ranged in age from 2 to 65 years (median = 14). Tumors were centered not only in the pons, thalamus, and spinal cord, but also in the third ventricle, hypothalamus, pineal region and cerebellum. Patients with pontine tumors were younger (median = 7 years) than those with thalamic (median = 24 years) or spinal (median = 25 years) tumors. A wide morphologic spectrum was encountered including gliomas with giant cells, epithelioid and rhabdoid cells, primitive neuroectodermal tumor (PNET)-like foci, neuropil-like islands, pilomyxoid features, ependymal-like areas, sarcomatous transformation, ganglionic differentiation and pleomorphic xanthoastrocytoma (PXA)-like areas. In this series, histone H3-K27M mutation was mutually exclusive with IDH1 mutation and EGFR amplification, rarely co-occurred with BRAF-V600E mutation, and was commonly associated with p53 overexpression, ATRX loss (except in pontine gliomas), and monosomy 10.
AB - Somatic mutations of the H3F3A and HIST1H3B genes encoding the histone H3 variants, H3.3 and H3.1, were recently identified in high-grade gliomas arising in the thalamus, pons and spinal cord of children and young adults. However, the complete range of patients and locations in which these tumors arise, as well as the morphologic spectrum and associated genetic alterations remain undefined. Here, we describe a series of 47 diffuse midline gliomas with histone H3-K27M mutation. The 25 male and 22 female patients ranged in age from 2 to 65 years (median = 14). Tumors were centered not only in the pons, thalamus, and spinal cord, but also in the third ventricle, hypothalamus, pineal region and cerebellum. Patients with pontine tumors were younger (median = 7 years) than those with thalamic (median = 24 years) or spinal (median = 25 years) tumors. A wide morphologic spectrum was encountered including gliomas with giant cells, epithelioid and rhabdoid cells, primitive neuroectodermal tumor (PNET)-like foci, neuropil-like islands, pilomyxoid features, ependymal-like areas, sarcomatous transformation, ganglionic differentiation and pleomorphic xanthoastrocytoma (PXA)-like areas. In this series, histone H3-K27M mutation was mutually exclusive with IDH1 mutation and EGFR amplification, rarely co-occurred with BRAF-V600E mutation, and was commonly associated with p53 overexpression, ATRX loss (except in pontine gliomas), and monosomy 10.
KW - DIPG
KW - H3F3A
KW - HIST1H3B
KW - K27M mutation
KW - astrocytoma
KW - diffuse intrinsic pontine glioma
KW - diffuse midline glioma
KW - glioblastoma
KW - histone H3.1
KW - histone H3.3
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U2 - 10.1111/bpa.12336
DO - 10.1111/bpa.12336
M3 - Article
C2 - 26517431
AN - SCOPUS:84988584592
SN - 1015-6305
VL - 26
SP - 569
EP - 580
JO - Brain Pathology
JF - Brain Pathology
IS - 5
ER -