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.