دورية أكاديمية
أعرض في EDS

Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma.

التفاصيل البيبلوغرافية
العنوان: Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma.
المؤلفون: Xu F; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Viaene AN; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ruiz J; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Schubert J; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Wu J; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Chen J; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Cao K; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Fu W; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Bagatell R; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Fan Z; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Long A; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Pagliaroli L; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Zhong Y; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Luo M; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Kreiger PA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Surrey LF; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Wertheim GB; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Cole KA; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Li MM; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA. lim5@chop.edu.; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. lim5@chop.edu.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. lim5@chop.edu., Santi M; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA. santim@chop.edu.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. santim@chop.edu., Storm PB; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. storm@chop.edu.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. storm@chop.edu.
المصدر: Acta neuropathologica communications [Acta Neuropathol Commun] 2022 Jul 14; Vol. 10 (1), pp. 102. Date of Electronic Publication: 2022 Jul 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2013]-
مواضيع طبية MeSH: Sarcoma*/genetics , Sarcoma*/pathology , Sarcoma, Small Cell*/diagnosis , Sarcoma, Small Cell*/genetics , Sarcoma, Small Cell*/pathology , Soft Tissue Neoplasms*/genetics, Ataxin-1/genetics ; Biomarkers, Tumor/genetics ; Gene Expression ; Humans ; Infant ; Methylation ; Oncogene Proteins, Fusion/genetics ; Repressor Proteins/genetics ; Retrospective Studies ; Transcription Factors/genetics
مستخلص: CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of "CIC-rearranged" sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases.
(© 2022. The Author(s).)
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معلومات مُعتمدة: T32 CA009679 United States CA NCI NIH HHS; U2CHL138346 Foundation for the National Institutes of Health
فهرسة مساهمة: Keywords: ATXN1/ATXN1L-associated fusions; CIC-rearranged sarcoma; Whole transcriptome sequencing
المشرفين على المادة: 0 (ATXN1 protein, human)
0 (ATXN1L protein, human)
0 (Ataxin-1)
0 (Biomarkers, Tumor)
0 (Oncogene Proteins, Fusion)
0 (Repressor Proteins)
0 (Transcription Factors)
تواريخ الأحداث: Date Created: 20220714 Date Completed: 20220718 Latest Revision: 20221022
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9281131
DOI: 10.1186/s40478-022-01401-z
PMID: 35836290
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-5960
DOI:10.1186/s40478-022-01401-z