title: NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.
abstract: CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion.
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sugita
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Aoyama
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Mukai
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Hama
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido 060-8543, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Emori
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido 060-8543, Japan. Electronic address: hasetada@sapmed.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D049109:Cell Proliferation; D018450:Disease Progression; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D050939:Gene Fusion; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C498610:CIC protein, human; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715631:NKX2-2 protein, human; C000622834:NUTM2A-CIC fusion protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins; D014157:Transcription Factors
keywords: CIC; CIC-rearranged sarcoma; Fluorescence in situ hybridization; Immunohistochemistry; NUTM2A; NUTM2A-CIC fusion sarcoma; Next-generation sequencing