تقرير
Clinical whole-genome sequencing and FISH identify two different fusion partners for NUP98 in a patient with acute myeloid leukemia: A case report.
| العنوان: | Clinical whole-genome sequencing and FISH identify two different fusion partners for NUP98 in a patient with acute myeloid leukemia: A case report. |
|---|---|
| المؤلفون: | Mojarad BA; Cytogenetics and Molecular Pathology Lab, Division of Lab and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, MO, USA. Electronic address: bahareh@wustl.edu., Crees ZD; Division of Oncology, Department of Medicine, Washington University School of Medicine in Saint Louis, MO, USA., Schroeder MC; Cytogenetics and Molecular Pathology Lab, Division of Lab and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, MO, USA., Xiang Z; Division of Oncology, Department of Medicine, Washington University School of Medicine in Saint Louis, MO, USA., Vader J; Cardiovascular Division, Department of Medicine, Washington University School of Medicine in Saint Louis, MO, USA., Sina J; Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, MO, USA., Jacoby M; Division of Oncology, Department of Medicine, Washington University School of Medicine in Saint Louis, MO, USA., Frater JL; Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, MO, USA., Duncavage EJ; Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, MO, USA., Spencer DH; Division of Oncology, Department of Medicine, Washington University School of Medicine in Saint Louis, MO, USA., Lavine K; Cardiovascular Division, Department of Medicine, Washington University School of Medicine in Saint Louis, MO, USA., Neidich JA; Cytogenetics and Molecular Pathology Lab, Division of Lab and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, MO, USA; Department of Pediatrics, Washington University School of Medicine in Saint Louis, MO, USA., Amarillo I; Cytogenetics and Molecular Pathology Lab, Division of Lab and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, MO, USA. |
| المصدر: | Cancer genetics [Cancer Genet] 2024 Jan; Vol. 280-281, pp. 1-5. Date of Electronic Publication: 2023 Nov 29. |
| نوع المنشور: | Case Reports |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 101539150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2210-7762 (Print) NLM ISO Abbreviation: Cancer Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Elsevier |
| مواضيع طبية MeSH: | Leukemia, Myeloid, Acute*/genetics, Female ; Humans ; Middle Aged ; In Situ Hybridization, Fluorescence ; Base Sequence ; Nuclear Pore Complex Proteins/genetics ; Translocation, Genetic |
| مستخلص: | Background: Only rare cases of acute myeloid leukemia (AML) have been shown to harbor a t(8;11)(p11.2;p15.4). This translocation is believed to involve the fusion of NSD3 or FGFR1 with NUP98; however, apart from targeted mRNA quantitative PCR analysis, no molecular approaches have been utilized to define the chimeric fusions present in these rare cases. Case Presentation: Here we present the case of a 51-year-old female with AML with myelodysplastic-related morphologic changes, 13q deletion and t(8;11), where initial fluorescence in situ hybridization (FISH) assays were consistent with the presence of NUP98 and FGFR1 rearrangements, and suggestive of NUP98/FGFR1 fusion. Using a streamlined clinical whole-genome sequencing approach, we resolved the breakpoints of this translocation to intron 4 of NSD3 and intron 12 of NUP98, indicating NUP98/NSD3 rearrangement as the likely underlying aberration. Furthermore, our approach identified small variants in WT1 and STAG2, as well as an interstitial deletion on the short arm of chromosome 12, which were cryptic in G-banded chromosomes. Conclusions: NUP98 fusions in acute leukemia are predictive of poor prognosis. The associated fusion partner and the presence of co-occurring mutations, such as WT1, further refine this prognosis with potential clinical implications. Using a clinical whole-genome sequencing analysis, we resolved t(8;11) breakpoints to NSD3 and NUP98, ruling out the involvement of FGFR1 suggested by FISH while also identifying multiple chromosomal and sequence level aberrations. Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest or financial disclosures. (Copyright © 2023. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Acute myeloid leukemia; ChromoSeq; Fluorescence in situ hybridization; MyeloSeq; Nup98/nsd3 rearrangement; Targeted sequencing; Whole-genome sequencing |
| المشرفين على المادة: | 0 (nuclear pore complex protein 98) 0 (Nuclear Pore Complex Proteins) |
| تواريخ الأحداث: | Date Created: 20231206 Date Completed: 20240108 Latest Revision: 20240313 |
| رمز التحديث: | 20240314 |
| DOI: | 10.1016/j.cancergen.2023.11.001 |
| PMID: | 38056049 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder كن أول من يترك تعليقا!