Proteomics

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MYCN and MAX alterations in Wilms tumor and identification of novel interactors as biomarker candidates


ABSTRACT: Wilms tumor (WT) is the most common renal tumor in childhood. Among others, MYCN copy number gain and MYCN P44L and MAX R60Q mutations have been identified in WT. The proto-oncogene MYCN encodes a transcription factor that requires dimerization with MAX to activate transcription of numerous target genes. MYCN gain has been associated with adverse prognosis. The MYCN P44L and MAX R60Q mutations, located in either the transactivating or basic helix-loop-helix domain, respectively, are predicted to be damaging by different pathogenicity prediction tools. We screened a large cohort of unselected WTs and revealed frequencies of 3 % for MYCN P44L and 0.8 % for MAX R60Q, associated with a higher risk of relapse in the case of MYCN. Biochemical characterization identified a reduced transcriptional activation potential for MAX R60Q, while the MYCN P44L mutation did not change activation potential or protein stability. The protein interactome of N-MYC-P44L was likewise not altered as shown by mass spectrometric analyses of purified N-MYC complexes. Nevertheless, we could identify a number of novel N-MYC partner proteins, and several of these are known for their oncogenic potential. Correlated expression in WT samples suggests a role in WT oncogenesis and they expand the range of potential biomarkers for WT stratification and targeting, especially for high-risk WT.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Ovidio Jimenez Martin  

LAB HEAD: Manfred Gessler

PROVIDER: PXD025996 | Pride | 2022-02-17

REPOSITORIES: Pride

Dataset's files

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Action DRS
2019-01-31_Fusion_16676.raw Raw
2019-01-31_Fusion_16677.raw Raw
2019-01-31_Fusion_16678.raw Raw
2019-01-31_Fusion_16679.raw Raw
2019-01-31_Fusion_16680.raw Raw
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Publications

MYCN and MAX alterations in Wilms tumor and identification of novel N-MYC interaction partners as biomarker candidates.

Jiménez Martín Ovidio O   Schlosser Andreas A   Furtwängler Rhoikos R   Wegert Jenny J   Gessler Manfred M  

Cancer cell international 20211024 1


<h4>Background</h4>Wilms tumor (WT) is the most common renal tumor in childhood. Among others, MYCN copy number gain and MYCN P44L and MAX R60Q mutations have been identified in WT. MYCN encodes a transcription factor that requires dimerization with MAX to activate transcription of numerous target genes. MYCN gain has been associated with adverse prognosis in different childhood tumors including WT. The MYCN P44L and MAX R60Q mutations, located in either the transactivating or basic helix-loop-h  ...[more]

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