Receptor tyrosine kinase pathway analysis sheds light on similarities between clear-cell sarcoma and metastatic melanoma
| Autor: | Piero Picci, Marco Alberghini, Alessandro Gronchi, Silvana Pilotti, Valentina Mauro, Silvia Brich, Giuseppina F. Dusio, Marta Orsenigo, Marco A. Pierotti, Fabio Bozzi, Silvia Stacchiotti, Elena Conca, Giuseppe Pelosi, Tiziana Negri, Paolo G. Casali |
|---|---|
| Přispěvatelé: | Negri, Tiziana, Brich, Silvia, Conca, Elena, Bozzi, Fabio, Orsenigo, Marta, Stacchiotti, Silvia, Alberghini, Marco, Mauro, Valentina, Gronchi, Alessandro, Dusio, Giuseppina F., Pelosi, Giuseppe, Picci, Piero, Casali, Paolo G., Pierotti, Marco A, Pilotti, Silvana |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Neuroblastoma RAS viral oncogene homolog
Male Cancer Research Chromosomes Human Pair 22 Gene Expression Trisomy RNA-Binding Protein medicine.disease_cause Receptor tyrosine kinase Clear Cell Chromosome Duplication 80 and over Phosphorylation Melanoma Genetics Aged 80 and over Tumor RNA-Binding Proteins Sarcoma Middle Aged Receptor Protein-Tyrosine Kinase Lymphatic Metastasis Adult Aged Base Sequence Biomarkers Tumor Calmodulin-Binding Proteins Chromosomes Human Pair 8 Female Humans Receptor Protein-Tyrosine Kinases Sarcoma Clear Cell Sequence Analysis DNA Young Adult Pair 8 KRAS Sequence Analysis Human PDGFRB Biology Chromosomes Genetic medicine Protein kinase B PI3K/AKT/mTOR pathway Calmodulin-Binding Protein fungi Lymphatic Metastasi DNA medicine.disease Cancer research biology.protein Pair 22 RNA-Binding Protein EWS Biomarkers V600E |
| Popis: | To highlight possible similarities and differences in receptor tyrosine kinase (RTK) and downstream signalling activation profiles between clear-cell sarcomas (CCS) and metastatic melanomas (MM), frozen, and paired-matched fixed samples of six CCS with EWSR1 rearrangement (EWSR1+), five CCS without EWSR1 rearrangement (EWSR1-), and seven MM were investigated by means of biochemical, immunohistochemical, FISH, molecular analyses, and immunofluorescence confocal microscopy. Fixed samples of a further 10 CCS and 14 MM were investigated by means of sequencing for BRAF, NRAS, and KRAS mutations and FISH analyses for the gain of chromosomes 22 and 8. RTK analysis of all CCS/MM samples showed activation of short-form (sf) recepteur d'origine nantais (RON) RTK and of PDGFRB, MET, and HER3. Analysis of downstream signaling revealed consistent phosphorylation patterns of PI3K/AKT, RSK, and the mTOR targets S6 and 4EBP1. Analysis of frozen and fixed material from 21 CCS and 21 MM showed the presence of the V600E BRAF mutation in 2/12 EWSR1+ and 3/9 EWSR1- CCS and 9/21 MM and demonstrated a significant (P < 0.001) correlation between the gain of chromosomes 22 and 8 and EWSR1- CCS. Our results show that BRAF mutation can also be present in CCS and support the proposed aberration of chromosomes 22 and 8 as a possibly useful nonrandom hallmark of EWSR1- CCS. Besides, they broaden the spectrum of the similarities of RTK pathway activation between CCS and MM, thus suggesting that new drugs found to be active in melanoma and RON inhibitors could have a role in CCS treatment. © 2011 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|