Ataxin-1 is a DNA-binding protein that in humans is encoded by the ATXN1 gene. Mutations in ataxin-1 cause spinocerebellar ataxia type 1, an inherited neurodegenerative disease characterized by a progressive loss of cerebellar neurons, particularly Purkinje neurons.
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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. Satomi et al. reported 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 immune profile, the tumor was provisionally diagnosed as CIC-rearranged sarcoma. However, no CIC fusions or [[mutation]]s 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
((Satomi K, Ohno M, Kubo T, Honda-Kitahara M, Matsushita Y, Ichimura K, Narita Y, Ichikawa H, Yoshida A. Central nervous system sarcoma with ATXN1::DUX4 fusion expands the concept of CIC-rearranged sarcoma. Genes Chromosomes Cancer. 2022 Jun 17. doi: 10.1002/gcc.23080. Epub ahead of print. PMID: 35715887.)).