title: Intratumoral heterogeneity of genomic imbalance in a case of epithelioid glioblastoma with BRAF V600E mutation.
abstract: Epithelioid glioblastoma is among the rarest variants of glioblastoma and is not formally recognized in the World Health Organization classification; it is composed of monotonous, discohesive sheets of small, round cells with eccentric nuclei and eosinophilic cytoplasm devoid of cytoplasmic stellate processes, showing the retention of nuclear staining of INI-1 protein. Here, we report a case involving a 22-year-old man with a right occipital lobe tumor, which comprised mainly epithelioid tumor cells with a small area of diffusely infiltrating less atypical astrocytoma cells showing a lower cell density. Array comparative genomic hybridization separately performed for each histologically distinct component demonstrated eight shared copy number alterations (CNAs) and three CNAs observed only in epithelioid cells; one of the latter was a homozygous deletion of a tumor suppressor gene, LSAMP, at 3q13.31. BRAF V600E mutation was observed both in epithelioid tumor cells and in diffusely infiltrating less atypical astrocytoma cells. Our findings suggest that the regional loss of LSAMP led to the aggressive nature of epithelioid cells in the present case of epithelioid glioblastoma.
authors.affiliation: Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Nobusawa
authors.forename: Junko
authors.initials: J
authors.lastname: Hirato
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kurihara
authors.forename: Akira
authors.initials: A
authors.lastname: Ogawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Okura
authors.forename: Masaya
authors.initials: M
authors.lastname: Nagaishi
authors.forename: Hayato
authors.initials: H
authors.lastname: Ikota
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yokoo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D014633:Valine / Q000235:genetics*; D055815:Young Adult
chemical_list: D018698:Glutamic Acid; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine
keywords: BRAF; LSAMP; array CGH; epithelioid glioblastoma