Detection of prognostically relevant mutations and translocations in myeloid sarcoma by next generation sequencing

Kashofer, Karl; Gornicec, Max; Lind, Karin; Caraffini, Veronica; Schauer, Silvia; Beham‐Schmid, Christine; Wölfler, Albert; Höefler, Gerald; Sill, Heinz; Zebisch, Armin

doi:10.1080/10428194.2017.1339879

Cited by 43 publications

(27 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, MS shares the same mutation spectrum as AML, frequently involving RAS pathway, activated signals, DNA methylation, cohesins, splicing, transcription factors, chromatin modification and other myeloid neoplasm-related genes. NPM1 , NRAS , and DNMT3A are found to be most frequently mutated in AML [13]. The other affected genes include TET2 , FLT3 -ITD/TKD, PTPN11 , IDH2 , CSF3R , RUNX1 , GATA2 , and ASXL1 .…”

Section: Discussionmentioning

confidence: 99%

Rare myeloid sarcoma with KMT2A (MLL)-ELL fusion presenting as a vaginal wall mass

et al. 2019

View full text Add to dashboard Cite

Backgroud Myeloid sarcoma (MS) is a rare neoplasm of immature myeloid precursors that form tumor mass outside the bone marrow. The diagnosis of de novo MS can be challenging, particularly in patients with no prior history of hematologic malignancies or when MS involves unusual anatomic sites. Case presentation The patient was a 53-year-old woman with a history of uterine fibroids and vaginal bleeding for many years who presented with a vaginal wall mass. The tumor had histologic and phenotypic features of histiocytic sarcoma, however, overlapping with a possible extramedullary MS. Using a comprehensive genomic profiling, we were able to identify recurrent chromosomal aberrations associated with MS including a rare KMT2A - ELL fusion, losses of chromosomes 1p, 9, 10, 15, 18, and gain of chromosome 1q and mutations in FLT3 and PTPN11 , and achived the final diagnosis of a de novo MS. The patient received standard treatment for acute myeloid leukemia regimen with stem cell transplantation and achieved complete remission. Conclusion Our case illustrates the clinical utility of comprehensive genomic profiling in assisting the diagnosis or differential diagnosis of challenging MS or histiocytic sarcoma cases, and in providing important information in tumor biology for appropriate clinical management.

show abstract

Section: Discussionmentioning

confidence: 99%

Rare myeloid sarcoma with KMT2A (MLL)-ELL fusion presenting as a vaginal wall mass

et al. 2019

View full text Add to dashboard Cite

show abstract

“…There are some commercial strategies to detect fusion transcripts, but these approaches require the use of two different samples, DNA for mutations and RNA for fusion transcripts analysis, as well as two NGS protocols running in parallel. 22,23 Furthermore, the strategies based on RNA for the identification of the fusions do not allow the detection of many unknown rearrangements, and they will not be able to determine the exact breakpoint position when they are in intronic regions. The precise location of the breakpoints can be used as a target for minimal residual disease 14 detection, and the discovery of new rearrangements could guide clinical decisions in patients otherwise wrongly cataloged as normal karyotype.…”

Section: Discussionmentioning

confidence: 99%

A New Next-Generation Sequencing Strategy for the Simultaneous Analysis of Mutations and Chromosomal Rearrangements at DNA Level in Acute Myeloid Leukemia Patients

Prieto-Conde

Corchete

García‐Álvarez

et al. 2020

The Journal of Molecular Diagnostics

View full text Add to dashboard Cite

show abstract

“…NGS can detect genetic abnormalities in large panels of genes, which can also provide novel insight into molecular pathogenesis and targeted therapy of MS. Recent studies have focused on the detection of prognostically relevant mutations in MS by using a myeloid malignancy multigene mutation panel [18,19]. Wild-type tumor protein 53 (TP53) is a major tumor suppressor protein encoded by the TP53 gene located on the short arm (p) of chromosome 17.…”

Section: Discussionmentioning

confidence: 99%

Mediastinal Myeloid Sarcoma with TP53 Mutation Preceding Acute Myeloid Leukemia with a PICALM-MLLT10 Fusion Gene

Naesens¹,

Devos²,

Nollet³

et al. 2018

Acta Haematol

View full text Add to dashboard Cite

Introduction: Myeloid sarcoma (MS), previously known as granulocytic sarcoma or chloroma, is a rare neoplastic condition defined as a tumor mass consisting of myeloblasts or immature myeloid cells occurring at an extramedullary site. Clinical presentation is diverse and determined by a tumor mass effect or local organ dysfunction. Case Report: We report the case of a 25-year-old previously healthy male with rapidly progressive shortness of breath. A chest CT scan demonstrated a heterogenous anterosuperior mediastinal mass with pleural and pericardial invasion. A diagnosis of MS with both myeloid and lymphoid characteristics was made by pathologic, morphologic, and immunophenotypic investigation. Next generation analysis revealed a pathogenic TP53 mutation (c.1035_1036insCT, p.Glu346Leufs*25). After 4 cycles of chemotherapy only a partial metabolic response and tumor size reduction was obtained. A pretransplant bone marrow biopsy revealed the progression of disease to acute myeloid leukemia. Cytogenetic analysis demonstrated a t(10; 11)(p12;q21). Fluorescence in situ hybridization confirmed the presence of a PICALM-MLLT10 fusion gene. Conclusion: MS with a mediastinal localization is rare and often misdiagnosed as malignant lymphoma. Acute leukemia harboring a PICALM-MLLT10 fusion gene is characterized by a mixed T cell and myeloid phenotype. The rearrangement is a rare recurrent translocation associated with specific clinical features, as illustrated in this case report.

show abstract

Detection of prognostically relevant mutations and translocations in myeloid sarcoma by next generation sequencing

Cited by 43 publications

References 15 publications

Rare myeloid sarcoma with KMT2A (MLL)-ELL fusion presenting as a vaginal wall mass

Rare myeloid sarcoma with KMT2A (MLL)-ELL fusion presenting as a vaginal wall mass

A New Next-Generation Sequencing Strategy for the Simultaneous Analysis of Mutations and Chromosomal Rearrangements at DNA Level in Acute Myeloid Leukemia Patients

Mediastinal Myeloid Sarcoma with TP53 Mutation Preceding Acute Myeloid Leukemia with a PICALM-MLLT10 Fusion Gene

Contact Info

Product

Resources

About