دورية أكاديمية
Copy number aberrations of BCL2 and CDKN2A/B identified by array-CGH in thymic epithelial tumors
| العنوان: | Copy number aberrations of BCL2 and CDKN2A/B identified by array-CGH in thymic epithelial tumors |
|---|---|
| المؤلفون: | PETRINI, IACOPO, Meltzer, P. S., Zucali, P. A., Luo, J., Lee, C., Santoro, A., Lee, H. S., Killian, K. J., Wang, Y., Tsokos, M., Roncalli, M., Steinberg, S. M., Giaccone, G. |
| المساهمون: | Petrini, Iacopo, Meltzer, P. S., Zucali, P. A., Luo, J., Lee, C., Santoro, A., Lee, H. S., Killian, K. J., Wang, Y., Tsokos, M., Roncalli, M., Steinberg, S. M., Giaccone, G. |
| سنة النشر: | 2012 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | BCL2 anti-apoptotic family member, CDKN2A, comparative genomic hybridization, target therapy, thymic epithelial tumor, Adult, Aged, 80 and over, Algorithm, Aniline Compound, Animal, Apoptosis Regulatory Protein, Autophagy, Benzenesulfonate, Cell Line, Tumor, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variation, Female, Human, Male, Mice, Nude, Middle Aged, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasms, Glandular and Epithelial, Niacinamide |
| الوصف: | The molecular pathology of thymic epithelial tumors (TETs) is largely unknown. Using array comparative genomic hybridization (CGH), we evaluated 59 TETs and identified recurrent patterns of copy number (CN) aberrations in different histotypes. GISTIC algorithm revealed the presence of 126 significant peaks of CN aberration, which included 13 cancer-related genes. Among these peaks, CN gain of BCL2 and CN loss of CDKN2A/B were the only genes in the respective regions of CN aberration and were associated with poor outcome. TET cell lines were sensitive to siRNA knockdown of the anti-apoptotic molecules BCL2 and MCL1. Gx15-070, a pan-BCL2 inhibitor, induced autophagy-dependent necroptosis in TET cells via a mechanism involving mTOR pathways, and inhibited TET xenograft growth. ABT263, an inhibitor of BCL2/BCL-XL/BCL-W, reduced proliferation in TET cells when administered in combination with sorafenib, a tyrosine kinase inhibitor able to downregulate MCL1. Immunohistochemistry on 132 TETs demonstrated that CN loss of CDKN2A correlated with lack of expression of its related protein p16(INK4) and identified tumors with poor prognosis. The molecular markers BCL2 and CDKN2A may be of potential value in diagnosis and prognosis of TETs. Our study provides the first preclinical evidence that deregulated anti-apoptotic BCL2 family proteins may represent suitable targets for TET treatment. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/22825469; info:eu-repo/semantics/altIdentifier/wos/WOS:000306786400014; volume:3; issue:7; firstpage:e351; journal:CELL DEATH & DISEASE; http://hdl.handle.net/11568/757337Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84864882707 |
| DOI: | 10.1038/cddis.2012.92 |
| الإتاحة: | https://doi.org/10.1038/cddis.2012.92Test http://hdl.handle.net/11568/757337Test |
| رقم الانضمام: | edsbas.D83B095D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/cddis.2012.92 |
|---|