PMID- 35715887
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220923
IS  - 1098-2264 (Electronic)
IS  - 1045-2257 (Linking)
VI  - 61
IP  - 11
DP  - 2022 Nov
TI  - Central nervous system sarcoma with ATXN1::DUX4 fusion expands the concept of 
      CIC-rearranged sarcoma.
PG  - 683-688
LID - 10.1002/gcc.23080 [doi]
AB  - CIC-rearranged sarcoma is a high-grade sarcoma, most often harboring CIC::DUX4 
      fusion, and is characterized by a distinct round cell histology, co-expression of 
      ETV4 and WT1, and a specific DNA methylation class. Herein, we report a brain 
      tumor with ATXN1::DUX4 that had an indistinguishable phenotype and DNA 
      methylation profile from CIC-rearranged sarcoma. A 40-year-old man presented with 
      a 5 cm hemorrhagic mass in the right frontal lobe of the cerebrum. The tumor was 
      resected and histologically showed a dense proliferation of relatively 
      monomorphic round cells with multifocal myxoid changes. Immunohistochemically, 
      the tumor was diffusely positive for ETV4, WT1, and DUX4. Through classic 
      histomorphology and immunoprofile, the tumor was provisionally diagnosed as 
      CIC-rearranged sarcoma. However, no CIC fusions or mutations were identified 
      using CIC break-apart fluorescence in situ hybridization (FISH) or FoundationOne 
      CDx. Despite multiple surgeries and adjuvant chemoradiation therapy, the patient 
      succumbed 16 months after presentation. RNA exome sequencing detected an in-frame 
      intraexonic ATXN1 (exon 9)::DUX4 (exon 1) fusion, which was validated by reverse 
      transcription-polymerase chain reaction and ATXN1 FISH assay. Upon DNA 
      methylation analysis, the tumor matched with CIC-rearranged sarcoma both by the 
      Deutsche Krebsforschungszentrum classifier and t-distributed stochastic neighbor 
      embedding. Along with a recent report of a similar pediatric brain tumor, the 
      present case suggests that ATXN1::DUX4 is a recurrent alternative molecular event 
      in the sarcoma type that is presently defined by CIC rearrangement, which prompts 
      an expansion of the tumor concept.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Satomi, Kaishi
AU  - Satomi K
AD  - Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, 
      Japan.
FAU - Ohno, Makoto
AU  - Ohno M
AUID- ORCID: 0000-0001-8031-4306
AD  - Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 
      Tokyo, Japan.
FAU - Kubo, Takashi
AU  - Kubo T
AD  - Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, 
      Japan.
FAU - Honda-Kitahara, Mai
AU  - Honda-Kitahara M
AD  - Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 
      Tokyo, Japan.
FAU - Matsushita, Yuko
AU  - Matsushita Y
AD  - Department of Brain Disease Translational Research, Juntendo University Faculty 
      of Medicine, Tokyo, Japan.
FAU - Ichimura, Koichi
AU  - Ichimura K
AD  - Department of Brain Disease Translational Research, Juntendo University Faculty 
      of Medicine, Tokyo, Japan.
FAU - Narita, Yoshitaka
AU  - Narita Y
AD  - Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 
      Tokyo, Japan.
AD  - Rare Cancer Center, National Cancer Center Hospital, Tokyo, Japan.
FAU - Ichikawa, Hitoshi
AU  - Ichikawa H
AUID- ORCID: 0000-0003-0142-2240
AD  - Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, 
      Japan.
FAU - Yoshida, Akihiko
AU  - Yoshida A
AUID- ORCID: 0000-0002-3373-0099
AD  - Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, 
      Japan.
AD  - Rare Cancer Center, National Cancer Center Hospital, Tokyo, Japan.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220713
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (ATXN1 protein, human)
RN  - 0 (Ataxin-1)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Oncogene Proteins, Fusion)
SB  - IM
MH  - Ataxin-1/genetics
MH  - Biomarkers, Tumor/genetics
MH  - *Brain Neoplasms/genetics
MH  - Central Nervous System/chemistry/metabolism/pathology
MH  - *Central Nervous System Neoplasms
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Oncogene Proteins, Fusion/genetics/metabolism
MH  - *Sarcoma/genetics/pathology
MH  - *Sarcoma, Small Cell/genetics
MH  - *Soft Tissue Neoplasms/genetics
OTO - NOTNLM
OT  - ATXN1
OT  - CIC
OT  - DUX4
OT  - central nervous system
OT  - sarcoma
EDAT- 2022/06/19 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/06/18 00:13
PHST- 2022/06/08 00:00 [revised]
PHST- 2022/04/26 00:00 [received]
PHST- 2022/06/11 00:00 [accepted]
PHST- 2022/06/19 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/06/18 00:13 [entrez]
AID - 10.1002/gcc.23080 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 2022 Nov;61(11):683-688. doi: 10.1002/gcc.23080. Epub 
      2022 Jul 13.