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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2014

AutorInnen: Berghoff, AS; Birner, P; Streubel, B; Kenner, L; Preusser, M

Titel: ALK gene aberrations and the JUN/JUNB/PDGFR axis in metastatic NSCLC.

Quelle: APMIS. 2014; 122(9):867-872



Autor/innen der Vetmeduni Vienna:

Kenner Lukas

Diese Publikation wurde nicht im Namen der Vetmeduni Vienna erstellt und ist deshalb ausschließlich der persönlichen Publikationsliste des/der Autors/Autorin zugeordnet!


Abstract:
Anaplastic lymphoma kinase (ALK) gene aberrations are found in several tumor types including anaplastic large cell lymphoma (ALCL) and non-small cell lung cancer (NSCLC). Crizotinib, an inhibitor of ALK-fusion proteins, has shown clinical activity, but resistance mechanisms limit long-lasting disease control. It has been shown that ALK-NPM fusion upregulates platelet-derived growth factor receptor beta (PDGFRB) via JUN and transcription factor Jun B (JUNB) in ALCL. PDGFRB inhibition has been identified as therapy option for ALK-positive ALCL. Here, we investigated the ALK/JUN/JUNB/transcription factor Jun C (JUNC)/PDGFR axis in metastatic NSCLC with regard to ALK aberrations. We performed immunohistochemical analysis of platelet-derived growth factor receptor alpha (PDGFRA), PDGFRB, JUNB and JUNC expression in formalin-fixed, paraffin-embedded specimens of 15 NSCLC brain metastases (5 ALK translocations, 3 of them involving EML4, 5 ALK amplifications, 5 without ALK aberrations). We did not find a statistically significant difference in expression of PDGFRA, PDGFRB, JUNB or JUNC in tumor samples with normal ALK status, ALK amplification or ALK translocations (Kruskal-Wallis test p > 0.05). Interestingly, PDGFRB was not expressed in tumor cells (but in vascular and stromal cells) in any of our cases. Our data argue against PDGFRB activation in association with ALK gene aberrations in metastatic NSCLC and thus seem to imply differential pathobiological roles of ALK alterations in lung cancer and lymphoma, possibly depending on different fusion partner genes. These results may be relevant for targeted therapies, as they indicate that inhibition of PDGFRB in ALK translocated NSCLC seems to be no therapeutic opportunity.

Keywords Pubmed: Aged
Carcinoma, Non-Small-Cell Lung/genetics*
Cell Cycle Proteins/biosynthesis
Female
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms/genetics*
Lymphoma/genetics
MAP Kinase Kinase 4/biosynthesis
Male
Microtubule-Associated Proteins/biosynthesis
Middle Aged
Protein Kinase Inhibitors/therapeutic use
Protein-Tyrosine Kinases
Pyrazoles/therapeutic use
Pyridines/therapeutic use
Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
Receptor Protein-Tyrosine Kinases/genetics*
Receptor, Platelet-Derived Growth Factor alpha/biosynthesis
Receptor, Platelet-Derived Growth Factor beta/biosynthesis*
Serine Endopeptidases/biosynthesis
Transcription Factors/biosynthesis


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