Targeted next generation sequencing identifies clinically actionable mutations in patients with melanoma.
Journal Article (Clinical Trial;Journal Article)
Somatic sequencing of cancers has produced new insight into tumorigenesis, tumor heterogeneity, and disease progression, but the vast majority of genetic events identified are of indeterminate clinical significance. Here, we describe a NextGen sequencing approach to fully analyzing 248 genes, including all those of known clinical significance in melanoma. This strategy features solution capture of DNA followed by multiplexed, high-throughput sequencing and was evaluated in 31 melanoma cell lines and 18 tumor tissues from patients with metastatic melanoma. Mutations in melanoma cell lines correlated with their sensitivity to corresponding small molecule inhibitors, confirming, for example, lapatinib sensitivity in ERBB4 mutant lines and identifying a novel activating mutation of BRAF. The latter event would not have been identified by clinical sequencing and was associated with responsiveness to a BRAF kinase inhibitor. This approach identified focal copy number changes of PTEN not found by standard methods, such as comparative genomic hybridization (CGH). Actionable mutations were found in 89% of the tumor tissues analyzed, 56% of which would not be identified by standard-of-care approaches. This work shows that targeted sequencing is an attractive approach for clinical use in melanoma.
Full Text
Duke Authors
Cited Authors
- Jeck, WR; Parker, J; Carson, CC; Shields, JM; Sambade, MJ; Peters, EC; Burd, CE; Thomas, NE; Chiang, DY; Liu, W; Eberhard, DA; Ollila, D; Grilley-Olson, J; Moschos, S; Neil Hayes, D; Sharpless, NE
Published Date
- July 2014
Published In
Volume / Issue
- 27 / 4
Start / End Page
- 653 - 663
PubMed ID
- 24628946
Pubmed Central ID
- PMC4121659
Electronic International Standard Serial Number (EISSN)
- 1755-148X
Digital Object Identifier (DOI)
- 10.1111/pcmr.12238
Language
- eng
Conference Location
- England