title: Individualized chemotherapy for osteosarcoma and identification of gene mutations in osteosarcoma.
abstract: 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.
authors.affiliation: Department of Orthopedics, Xijing Hospital, Forth Military Medical University, No. 15 West Changle Road, Xincheng District, Xi'an, Shaanxi, 710032, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xiao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Haoqiang
authors.initials: H
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.forename: Guojing
authors.initials: G
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Haodong
authors.initials: H
authors.lastname: Zhu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Hongbin
authors.initials: H
authors.lastname: Fan
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Hu
authors.forename: Sujia
authors.initials: S
authors.lastname: Wu
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Yu
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000077143:Docetaxel; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D057285:Precision Medicine; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins; D043823:Taxoids; D000077143:Docetaxel