دورية
Molecular Genomic Profiling of Melanocytic Nevi
| العنوان: | Molecular Genomic Profiling of Melanocytic Nevi |
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| المؤلفون: | Colebatch, Andrew J., Ferguson, Peter, Newell, Felicity, Kazakoff, Stephen H., Witkowski, Tom, Dobrovic, Alexander, Johansson, Peter A., Saw, Robyn P.M., Stretch, Jonathan R., McArthur, Grant A., Long, Georgina V., Thompson, John F., Pearson, John V., Mann, Graham J., Hayward, Nicholas K., Waddell, Nicola, Scolyer, Richard A., Wilmott, James S. |
| المصدر: | Journal of Investigative Dermatology; August 2019, Vol. 139 Issue: 8 p1762-1768, 7p |
| مستخلص: | The benign melanocytic nevus is the most common tumor in humans and rarely transforms into cutaneous melanoma. Elucidation of the nevus genome is required to better understand the molecular steps of progression to melanoma. We performed whole genome sequencing on a series of 14 benign melanocytic nevi consisting of both congenital and acquired types. All nevi had driver mutations in the MAPK signaling pathway, either BRAFV600E or NRASQ61R/L. No additional definite driver mutations were identified. Somatic mutations in nevi with higher mutation loads showed a predominance of mutational signatures 7a and 7b, consistent with UVR exposure, whereas nevi with lower mutation loads (including all three congenital nevi) had a predominance of the ubiquitous signatures 1 and 5. Two nevi had mutations in promoter regions predicted to bind E26 transformation-specific family transcription factors, as well as subclonal mutations in the TERTpromoter. This paper presents whole genome data from melanocytic nevi. We confirm that UVR is involved in the etiology of a subset of nevi. This study also establishes that TERTpromoter mutations are present in morphologically benign skin nevi in subclonal populations, which has implications regarding the interpretation of this emerging biomarker in sensitive assays. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 0022202X 15231747 |
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| DOI: | 10.1016/j.jid.2018.12.033 |