التفاصيل البيبلوغرافية
| العنوان: |
The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models |
| المؤلفون: |
Yen, Jennifer, White, Richard M, Wedge, David C, Van Loo, Peter, de Ridder, Jeroen, Capper, Amy, Richardson, Jennifer, Jones, David, Raine, Keiran, Watson, Ian R, Wu, Chang-Jiun, Cheng, Jiqiu, Martincorena, Iñigo, Nik-Zainal, Serena, Mudie, Laura, Moreau, Yves, Marshall, John, Ramakrishna, Manasa, Tarpey, Patrick, Shlien, Adam, Whitmore, Ian, Gamble, Steve, Latimer, Calli, Langdon, Erin, Kaufman, Charles, Dovey, Mike, Taylor, Alison, Menzies, Andy, McLaren, Stuart, O’Meara, Sarah, Butler, Adam, Teague, Jon, Lister, James, Chin, Lynda, Campbell, Peter, Adams, David J, Zon, Leonard I, Patton, E, Stemple, Derek L, Futreal, P |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2013 |
| المجموعة: |
BioMed Central |
| الوصف: |
Background Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS , which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53 , these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. Results To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF V600E or NRAS Q61K driven transgenic zebrafish lines. We find that engineered zebrafish melanomas show an overall low mutation burden, which has a strong, inverse association with the number of initiating germline drivers. Although tumors reveal distinct mutation spectrums, they show mostly C > T transitions without UV light exposure, and enrichment of mutations in melanogenesis, p53 and MAPK signaling. Importantly, a recurrent amplification occurring with pre-configured drivers BRAF V600E and p53 -/- suggests a novel path of BRAF cooperativity through the protein kinase A pathway. Conclusion This is the first analysis of a melanoma mutational landscape in the absence of UV light, where tumors manifest with remarkably low mutation burden and high heterogeneity. Genotype specific amplification of protein kinase A in cooperation with BRAF and p53 mutation suggests the involvement of melanogenesis in these . |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| العلاقة: |
http://genomebiology.com/2013/14/10/R113Test |
| الإتاحة: |
http://genomebiology.com/2013/14/10/R113Test |
| حقوق: |
Copyright 2013 Yen et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.469549E3 |
| قاعدة البيانات: |
BASE |
