黑色素瘤常规多重突变谱分析助力基因型驱动治疗试验入组

数据集获取（Figshare）

• 源站标题：Routine Multiplex Mutational Profiling of Melanomas Enables Enrollment in Genotype-Driven Therapeutic Trials
• DOI：10.1371/journal.pone.0035309
• 发布日期：2012-04-20
• 文件数：15 个
• 文件总体积：3.81 MB
• 源站页面：https://plos.figshare.com/articles/dataset/Routine_Multiplex_Mutational_Profiling_of_Melanomas_Enables_Enrollment_in_Genotype_Driven_Therapeutic_Trials/126040

命令行下载

curl -L -o "Figure_S1.tif" "https://ndownloader.figshare.com/files/334382"
curl -L -o "Figure_S2.tif" "https://ndownloader.figshare.com/files/334432"
curl -L -o "Figure_S3.tif" "https://ndownloader.figshare.com/files/334465"
curl -L -o "Methods_S1.docx" "https://ndownloader.figshare.com/files/334494"
curl -L -o "Table_S1.doc" "https://ndownloader.figshare.com/files/334724"
curl -L -o "Table_S2.doc" "https://ndownloader.figshare.com/files/334792"
curl -L -o "Table_S3.doc" "https://ndownloader.figshare.com/files/334858"
curl -L -o "Table_S4.doc" "https://ndownloader.figshare.com/files/334944"

文件清单

• Figure_S1.tif（1.76 MB）
• Figure_S2.tif（139.84 KB）
• Figure_S3.tif（196.28 KB）
• Methods_S1.docx（1.07 MB）
• Table_S1.doc（52.74 KB）
• Table_S2.doc（52.74 KB）
• Table_S3.doc（74.75 KB）
• Table_S4.doc（68.61 KB）
• Table_S5.doc（44.54 KB）
• Table_S6.doc（56.32 KB）
• Table_S7.doc（92.67 KB）
• Table_S8.doc（62.98 KB）
• Table_S9.doc（56.32 KB）
• Table_S10.docx（37.95 KB）
• Table_S11.doc（40.45 KB）

文件总体积 3.81 MB（源站 API 实测）。

数据说明

Purpose
Knowledge of tumor mutation status is becoming increasingly important for the treatment of cancer, as mutation-specific inhibitors are being developed for clinical use that target only sub-populations of patients with particular tumor genotypes. Melanoma provides a recent example of this paradigm. We report here development, validation, and implementation of an assay designed to simultaneously detect 43 common somatic point mutations in 6 genes (BRAF, NRAS, KIT, GNAQ, GNA11, and CTNNB1) potentially relevant to existing and emerging targeted therapies specifically in melanoma.
Methods
The test utilizes the SNaPshot method (multiplex PCR, multiplex primer extension, and capillary electrophoresis) and can be performed rapidly with high sensitivity (requiring 5–10% mutant allele frequency) and minimal amounts of DNA (10–20 nanograms). The assay was validated using cell lines, fresh-frozen tissue, and formalin-fixed paraffin embedded tissue. Clinical characteristics and the impact on clinical trial enrollment were then assessed for the first 150 melanoma patients whose tumors were genotyped in the Vanderbilt molecular diagnostics lab.
Results
Directing this test to a single disease, 90 of 150 (60%) melanomas from sites throughout the body harbored a mutation tested, including 57, 23, 6, 3, and 2 mutations in BRAF, NRAS, GNAQ, KIT, and CTNNB1, respectively. Among BRAF V600 mutations, 79%, 12%, 5%, and 4% were V600E, V600K, V600R, and V600M, respectively. 23 of 54 (43%) patients with mutation harboring metastatic disease were subsequently enrolled in genotype-driven trials.
Conclusion
We present development of a simple mutational profiling screen for clinically relevant mutations in melanoma. Adoption of this genetically-informed approach to the treatment of melanoma has already had an impact on clinical trial enrollment and prioritization of therapy for patients with the disease.

许可

CC BY 4.0

引用

学术使用请引用 DOI 10.1371/journal.pone.0035309（source: https://plos.figshare.com/articles/dataset/Routine_Multiplex_Mutational_Profiling_of_Melanomas_Enables_Enrollment_in_Genotype_Driven_Therapeutic_Trials/126040）。