Individualized chemotherapy for osteosarcoma and identification of gene mutations in osteosarcoma
The study aims to identify novel gene mutations in osteosarcoma and to guide individualized preoperative chemotherapy for osteosarcoma based on the analysis of expression and mutations of the drug-metabolism-related genes. Twenty-eight osteosarcoma patients received individualized preoperative chemotherapy regimens. Expression levels and mutations of chemotherapy-related genes in samples collected from the patients were determined using real-time PCR and DNA sequencing, respectively. Patient sensitivity to chemotherapeutic agents was evaluated by systematic analysis of the PCR and sequencing results. Novel mutations were identified via high-throughput sequencing of 339 genes in 10 osteosarcoma samples. Individualized preoperative chemotherapy outcomes were valid for nine patients (n = 9/28, 32.1 %). Chemosensitivity assays showed that all 28 patients were sensitive to ifosfamide, whereas 46.4 and 39.2 % were sensitive to docetaxel and platinum, respectively. More importantly, patients receiving highly chemosensitive chemotherapy agents had better prognosis and treatment outcomes than those receiving less chemosensitive agents (P < 0.05). In addition, 39 gene mutations were detected in at least five osteosarcoma tumor samples. Analysis of the expression and mutation of drug-metabolism-related genes will aid in the design of effective individualized preoperative chemotherapy regimens for osteosarcoma. Determining the chemosensitivity of individual tumors to chemotherapeutic agents will facilitate the development of better therapeutic approaches. Individualized treatment of osteosarcoma may improve chemotherapy efficacy and the survival rate of osteosarcoma patients. High-throughput genotyping allows mapping of osteosarcoma mutations, and novel gene mutations offered new candidates for diagnosis and therapeutic targeting.
KeywordsOsteosarcoma Gene mutation High-throughput sequencing Individualized treatment
This study was supported by Natural Science Foundation of China (No. 31170914).
Conflicts of interest
- 21.Kudawara I, Aoki Y, Ueda T, Araki N, Naka N, Nakanishi H, et al. Neoadjuvant and adjuvant chemotherapy with high-dose ifosfamide, doxorubicin, cisplatin and high-dose methotrexate in non-metastatic osteosarcoma of the extremities: a phase II trial in japan. J Chemother. 2013;25:41–8.CrossRefPubMedGoogle Scholar
- 25.Liu C, Dai G, Zhang X. Chemosensitivity test for human osteosarcoma cells. Zhonghua zhong liu za zhi Chinese J Oncol. 1996;18:445–7.Google Scholar
- 31.Geller DS, Gorlick R. Osteosarcoma: A review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol : H&O. 2010;8:705–18.Google Scholar