Molecular characterization of <i>KMT2A</i> fusion partner genes in 13 cases of pediatric leukemia with complex or cryptic karyotypes

Garcia, Daniela Ribeiro Ney; Souza, Mariana Tavares de; Figueiredo, Amanda Faria de; Rittscher, Katharina; Abdelhay, Eliana; Matos, Roberto R. Capela de; Meyer, Claus; Marschalek, Rolf; Land, Marcelo Gerardin Poirot; Liehr, Thomas; Ribeiro, Raul C.; Silva, Maria Luiza Macedo

doi:10.1002/hon.2299

Cited by 11 publications

(11 citation statements)

References 22 publications

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“…Interestingly, CRK is higher expressed in all papillary type 1 pRCCs compared with other subtypes, yet no further CRK fusion has been detected in this ppRCC cohort. The phosphatidylinositol transfer protein alpha ( PITPNA ) gene has also been shown to be involved in oncogenesis as a fusion gene partner of MLL ( KMT2A ) in pediatric leukemia ( Ney Garcia et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

The genomic landscape of pediatric renal cell carcinomas

et al. 2022

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Section: Discussionmentioning

confidence: 99%

The genomic landscape of pediatric renal cell carcinomas

et al. 2022

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“…However, WBP1L expression had a 2.8-fold increase in the E/R subtype 55 , which coincides with the overexpression of SOX11 in the same subtype and may suggest co-regulation. MLLT11 is involved in lymphoid regulation and is a known partner gene in rare leukemia translocations 56,57 . Similarly, Coiled-coil domain containing 28 A (CCDC28A) is a fusion partner to NUP98 in AML 58 .…”

Section: Sox11 Expression Is Associated With a Favorable Outcomementioning

confidence: 99%

Clinicopathological features and prognostic value of SOX11 in childhood acute lymphoblastic leukemia

Grönroos

Mäkinen

Laukkanen

et al. 2020

Sci Rep

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Acute lymphoblastic leukemia is marked by aberrant transcriptional features that alter cell differentiation, self-renewal, and proliferative features. We sought to identify the transcription factors exhibiting altered and subtype-specific expression patterns in BALL and report here that SOX11, a developmental and neuronal transcription factor, is aberrantly expressed in the ETV6-RUNX1 and TCF3-PBX1 subtypes of acute B-cell leukemias. We show that a high expression of SOX11 leads to alterations of gene expression that are typically associated with cell adhesion, migration, and differentiation. A high expression is associated with DNA hypomethylation at the SOX11 locus and a favorable outcome. The results indicate that SOX11 expression marks a group of patients with good outcomes and thereby prompts further study of its use as a biomarker. SOX11 is a transcription factor (TF) encoded by the SOX11 gene located in chromosome 2p25 1. It is a member of the SoxC (sex-determining region Y-related HMG box) group of genes and consists of two functional domains-the N-terminal DNA-binding and the C-terminal transactivation domains 2,3. Other SoxC family members include SOX4 and SOX12. Of these, SOX4 is a crucial TF in B lymphopoiesis and is expressed in the Band T-cell lineages 2,4,5. SOX11 is normally expressed in the developing central nervous system of the embryo, in keratinocytes, and in some other epithelial tissues 1,6-8. It is also expressed in ovarian and breast cancer, in which both tumor suppressor and oncogenic functions have been suggested 9,10. A knockout mouse model revealed the vital role of SOX11 during embryonic development, as SOX11-deficient mice died after birth likely from multiple heart defects, asplenia, and organ hypoplasia in the lungs, stomach, and pancreas 11. SOX11 deletions and mutations are associated with neurodevelopmental disorders 12. Previous studies have shown that SOX11 mRNA and nuclear protein expression is a specific marker for conventional but not indolent mantle cell lymphoma (MCL) 8,13-15. In MCL, SOX11 has been associated with either increased or reduced cell proliferation 16-23 and either good or bad prognosis 24-27. In a cohort of 50 adult acute myeloid leukemia (AML) patients, a high SOX11 expression was associated with FLT/ITD and NPM1 mutations and a shortened disease-free survival 28. There is other evidence linking SOX11 with B-lineage malignancies. Dictor et al. (2009) reported that the nuclear expression of SOX11 was found in eight cases of B-lymphoblastic neoplasias 29. Another study reported the strong nuclear expression of SOX11 in a single B-cell and five T-cell lymphoblastic lymphoma/leukemias 13. Vegliante et al. (2011) demonstrated the increased expression of SOX11 mRNA in ETV6-RUNX1 (E/R) and

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“…Some form of the fusion has been reported in 18% of the pediatric AML patients and 6-8% pediatric ALL patients, respectively, [47,48]. In a study on 13 patients with KMT2A fusions, the KMT2A/MLLT3 gene fusion was present in 38% of the patients [49]. Small-molecule inhibitors, such as DOT1L, against KMT2A fusion-interacting proteins, are producing promising results in mixed lineage leukemia (MLL) [50] (Figure 2 (f)).…”

Section: Gene Fusionsmentioning

confidence: 99%

Origins and clinical relevance of proteoforms in pediatric malignancies

Lorentzian

Uzozie

Lange

2019

Expert Review of Proteomics

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Introduction: Cancer changes the proteome in complex ways that reach well beyond simple changes in protein abundance. Genomic and transcriptional variations and post-translational protein modification create functional variants of a protein, known as proteoforms. Childhood cancers have fewer genomic alterations but show equally dramatic phenotypic changes as malignant cells in adults. Therefore, unraveling the complexities of the proteome is even more important in pediatric malignancies. Areas covered: In this review, the biological origins of proteoforms and technological advancements in the study of proteoforms are discussed. Particular emphasis is given to their implication in childhood malignancies and the critical role of cancer-specific proteoforms for the next generation of cancer therapies and diagnostics. Expert opinion: Recent advancements in technology have led to a better understanding of the underlying mechanisms of tumorigenesis. This has been critical for the development of more effective and less harmful treatments that are based on direct targeting of altered proteins and deregulated pathways. As proteome coverage and the ability to detect complex proteoforms increase, the most need for change is in data compilation and database availability to mediate high-level data analysis and allow for better functional annotation of proteoforms.

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Molecular characterization of KMT2A fusion partner genes in 13 cases of pediatric leukemia with complex or cryptic karyotypes

Cited by 11 publications

References 22 publications

The genomic landscape of pediatric renal cell carcinomas

The genomic landscape of pediatric renal cell carcinomas

Clinicopathological features and prognostic value of SOX11 in childhood acute lymphoblastic leukemia

Origins and clinical relevance of proteoforms in pediatric malignancies

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