Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma
| Autor: | Natalia Gonzalez-Paz, Marta Chesi, Tae-Hoon Chung, George Mulligan, Siok Bian Ng, T Troska-Price, Wee Joo Chng, P L Bergsagel, Gaofeng Huang, R Fonseca |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
medicine.medical_specialty Myeloma MYC Biology Monoclonal Gammopathy of Undetermined Significance Article Bortezomib Proto-Oncogene Proteins c-myc 03 medical and health sciences 0302 clinical medicine immune system diseases Internal medicine hemic and lymphatic diseases medicine Humans Multiple myeloma 030304 developmental biology 0303 health sciences Hematology Gene Expression Profiling Cell Cycle Hyperdiploid Cell cycle medicine.disease Boronic Acids 3. Good health Gene expression profiling Survival Rate Cell Transformation Neoplastic Oncology 030220 oncology & carcinogenesis Pyrazines Mutation Proteasome inhibitor Cancer research ras Proteins MGUS Immunohistochemistry Multiple Myeloma Monoclonal gammopathy of undetermined significance medicine.drug |
| Zdroj: | Leukemia |
| ISSN: | 1476-5551 |
| Popis: | Events mediating transformation from the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are unknown. We analyzed a gene expression datasets generated on the Affymetrix U133 platform from 22 MGUS and 101 MM patients using gene-set enrichment analysis. Genes over-expressed in MM were enriched for cell cycle, proliferation and MYC activation gene-sets. Upon dissecting the relationship between MYC and cell cycle genesets, we identified and validated a MYC activation signature dissociated from proliferation. Applying this signature, MYC is activated in 67% of myeloma, but not in MGUS. This was further confirmed by immunohistochemistry using membrane CD138 and nuclear MYC double staining. We also showed that almost all tumors with RAS mutations expressed the MYC activation signature, and multiple mechanisms may be involved in activating MYC. MYC activation, whether assessed by gene expression signature or immunohistochemistry is associated with hyperdiploid MM, and shorter survival even in tumors that are not proliferative. Bortezomib treatment is able to overcome the survival disadvantage in patients with MYC activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|