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| Status |
Public on Jul 06, 2018 |
| Title |
Drug sensitivity screening and genomic characterization of 45 HPV-negative head and neck carcinoma cell lines for novel biomarkers of drug efficacy [CGH] |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
There is an unmet need for effective targeted therapies for patients with advanced head and neck squamous cell carcinoma (HNSCC). We correlated gene expression, gene copy numbers, and point mutations in 45 human papillomavirus-negative HNSCC cell lines with the sensitivity to 220 anticancer drugs to discover predictive associations to genetic alterations. The drug response profiles revealed diverse efficacy of the tested drugs across the cell lines. Several genomic abnormalities and gene expression differences were associated with response to mTOR, MEK, and EGFR inhibitors. NOTCH1 and FAT1 were the most commonly mutated genes after TP53 and also showed some association with response to MEK and/or EGFR inhibitors. MYC amplification and FAM83H overexpression associated with sensitivity to EGFR inhibitors, and PTPRD deletion with poor sensitivity to MEK inhibitors. The connection between high FAM83H expression and responsiveness to the EGFR inhibitor erlotinib was validated by gene silencing and from the data set at the Cancer Cell Line Encyclopedia. The data provide several novel genomic alterations that associated to the efficacy of targeted drugs in HNSCC. These findings require further validation in experimental models and clinical series.
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| Overall design |
Two-color experiment. DNA from forty-five head and neck squamous cell carcinoma UT-SCC cell lines were hybridized each against Human Reference Female or Male DNA (Agilent).
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| Contributor(s) |
Lepikhova T, Karhemo P, Louhimo R, Yadav B, Murumägi A, Kulesskiy E, Kivento M, Sihto H, Grénman R, Syrjänen SM, Kallioniemi O, Aittokallio T, Wennerberg K, Joensuu H, Monni O |
| Citation(s) |
33803266 |
| |
| Submission date |
Dec 11, 2017 |
| Last update date |
Apr 20, 2021 |
| Contact name |
Outi Monni |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Helsinki
|
| Department |
Research Programs Unit
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| Street address |
Haartmaninkatu 8
|
| City |
Helsinki |
| ZIP/Postal code |
00290 |
| Country |
Finland |
| |
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| Platforms (1) |
| GPL9128 |
Agilent-014693 Human Genome CGH Microarray 244A (Probe name version) |
|
| Samples (45)
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| This SubSeries is part of SuperSeries: |
| GSE108062 |
Drug sensitivity screening and genomic characterization of 45 HPV-negative head and neck carcinoma cell lines for novel biomarkers of drug efficacy |
|
| Relations |
| BioProject |
PRJNA421949 |
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