دورية أكاديمية
Identification and clinical impact of potentially actionable somatic oncogenic mutations in solid tumor samples
| العنوان: | Identification and clinical impact of potentially actionable somatic oncogenic mutations in solid tumor samples |
|---|---|
| المؤلفون: | Toomey, Sinead, Carr, Aoife, Mezynski, Mateusz Janusz, Elamin, Yasir, Rafee, Shereen, Cremona, Mattia, Morgan, Clare, Madden, Stephen, Abdul-Jalil, Khairun I., Gately, Kathy, Farrelly, Angela, Kay, Elaine W., Kennedy, Susan, O'Byrne, Kenneth, Grogan, Liam, Breathnach, Oscar, Morris, Patrick G., Eustace, Alexander J., Fay, Joanna, Cummins, Robert, O'Grady, Anthony, Kalachand, Roshni, O'Donovan, Norma, Kelleher, Fergal, O'Reilly, Aine, Doherty, Mark, Crown, John, Hennessy, Bryan T. |
| المصدر: | Journal of Translational Medicine |
| بيانات النشر: | BioMed Central Ltd. |
| سنة النشر: | 2020 |
| المجموعة: | Queensland University of Technology: QUT ePrints |
| الوصف: | Background: An increasing number of anti-cancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Successful use of these therapies is dependent on the presence or absence of somatic mutations within the patient's tumor that can confer clinical efficacy or drug resistance. Methods: The aim of our study was to determine the type, frequency, overlap and functional proteomic effects of potentially targetable recurrent somatic hotspot mutations in 47 cancer-related genes in multiple disease sites that could be potential therapeutic targets using currently available agents or agents in clinical development. Results: Using MassArray technology, of the 1300 patient tumors analysed 571 (43.9%) had at least one somatic mutation. Mutations were identified in 30 different genes. KRAS (16.5%), PIK3CA (13.6%) and BRAF (3.8%) were the most frequently mutated genes. Prostate (10.8%) had the lowest number of somatic mutations identified, while no mutations were identified in sarcoma. Ocular melanoma (90.6%), endometrial (72.4%) and colorectal (66.4%) tumors had the highest number of mutations. We noted high concordance between mutations in different parts of the tumor (94%) and matched primary and metastatic samples (90%). KRAS and BRAF mutations were mutually exclusive. Mutation co-occurrence involved mainly PIK3CA and PTPN11, and PTPN11 and APC. Reverse Phase Protein Array (RPPA) analysis demonstrated that PI3K and MAPK signalling pathways were more altered in tumors with mutations compared to wild type tumors. Conclusions: Hotspot mutational profiling is a sensitive, high-Throughput approach for identifying mutations of clinical relevance to molecular based therapeutics for treatment of cancer, and could potentially be of use in identifying novel opportunities for genotype-driven clinical trials. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://eprints.qut.edu.au/205015/1/68720006.pdfTest; Toomey, Sinead, Carr, Aoife, Mezynski, Mateusz Janusz, Elamin, Yasir, Rafee, Shereen, Cremona, Mattia, Morgan, Clare, Madden, Stephen, Abdul-Jalil, Khairun I., Gately, Kathy, Farrelly, Angela, Kay, Elaine W., Kennedy, Susan, O'Byrne, Kenneth, Grogan, Liam, Breathnach, Oscar, Morris, Patrick G., Eustace, Alexander J., Fay, Joanna, Cummins, Robert, O'Grady, Anthony, Kalachand, Roshni, O'Donovan, Norma, Kelleher, Fergal, O'Reilly, Aine, Doherty, Mark, Crown, John, & Hennessy, Bryan T. (2020) Identification and clinical impact of potentially actionable somatic oncogenic mutations in solid tumor samples. Journal of Translational Medicine, 18(1), Article number: 99.; https://eprints.qut.edu.au/205015Test/ |
| الإتاحة: | https://doi.org/10.1186/s12967-020-02273-4Test https://eprints.qut.edu.au/205015Test/ |
| حقوق: | free_to_read ; http://creativecommons.org/licenses/by/4.0Test/ ; 2020 The Author(s) ; This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au |
| رقم الانضمام: | edsbas.6F55636 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |