دورية أكاديمية
The stable traits of melanoma genetics: an alternate approach to target discovery
| العنوان: | The stable traits of melanoma genetics: an alternate approach to target discovery |
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| المؤلفون: | Spivey Tara L, De Giorgi Valeria, Zhao Yingdong, Bedognetti Davide, Pos Zoltan, Liu Qiuzhen, Tomei Sara, Ascierto Maria, Uccellini Lorenzo, Reinboth Jennifer, Chouchane Lotfi, Stroncek David F, Wang Ena, Marincola Francesco M |
| المصدر: | BMC Genomics, Vol 13, Iss 1, p 156 (2012) |
| بيانات النشر: | BMC, 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Biotechnology LCC:Genetics |
| مصطلحات موضوعية: | Melanoma, Melanoma genetics, Cancer, Tumor microenvironment, Biotechnology, TP248.13-248.65, Genetics, QH426-470 |
| الوصف: | Abstract Background The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number. Results Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis. Conclusions This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1471-2164 |
| العلاقة: | http://www.biomedcentral.com/1471-2164/13/156Test; https://doaj.org/toc/1471-2164Test |
| DOI: | 10.1186/1471-2164-13-156 |
| الوصول الحر: | https://doaj.org/article/e21adb9af1974b2480f274cad75f9f93Test |
| رقم الانضمام: | edsdoj.21adb9af1974b2480f274cad75f9f93 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14712164 |
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| DOI: | 10.1186/1471-2164-13-156 |