Osteosarcoma is a genetically unstable malignancy that most frequently occurs in children and young adults.The lack of progress in managing this devastating disease in the clinic has prompted international researchers...Osteosarcoma is a genetically unstable malignancy that most frequently occurs in children and young adults.The lack of progress in managing this devastating disease in the clinic has prompted international researchers to collaborate to profile key genomic alterations that define osteosarcoma.A team of researchers and clinicians from China,Finland,and the United States investigated human osteosarcoma by integrating transcriptome sequencing(RNA-seq),high-density genome-wide array comparative genomic hybridization(a CGH),fluorescence in situ hybridization(FISH),reverse transcription-polymerase chain reaction(RT-PCR),Sanger sequencing,cell culture,and molecular biological approaches.Systematic analysis of genetic/genomic alterations and further functional studies have led to several important findings,including novel rearrangement hotspots,osteosarcoma-specific LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes,VEGF and Wnt signaling pathway alterations,deletion of the WWOX gene,and amplification of the APEX1 and RUNX2 genes.Importantly,these genetic events associate significantly with pathogenesis,prognosis,progression,and therapeutic activity in osteosarcoma,suggesting their potential impact on improved managements of human osteosarcoma.This international initiative provides opportunities for developing new treatment modalities to conquer osteosarcoma.展开更多
基金partly supported by grants from the National Natural Science Foundation of China(81372872 to JY,81402215 to XD,and 81320108022 to KC)the University Cancer Foundation via the Sister Institution Network Fund(SINF)(to JY and WZ)+2 种基金the Program for Changjiang Scholars and Innovative Research Teamin University(PCSIRT)in China(IRT1076 to JY and KC)the Liddy Shriver Sarcoma Initiative(to JY and WZ),and the National Key Scientific and Technological Project(2011ZX09307-001-04 to KC)The Tissue Bank of Tianjin Medical University Cancer Institute&Hospital is partially supported by the National Foundation for Cancer Research(US)
文摘Osteosarcoma is a genetically unstable malignancy that most frequently occurs in children and young adults.The lack of progress in managing this devastating disease in the clinic has prompted international researchers to collaborate to profile key genomic alterations that define osteosarcoma.A team of researchers and clinicians from China,Finland,and the United States investigated human osteosarcoma by integrating transcriptome sequencing(RNA-seq),high-density genome-wide array comparative genomic hybridization(a CGH),fluorescence in situ hybridization(FISH),reverse transcription-polymerase chain reaction(RT-PCR),Sanger sequencing,cell culture,and molecular biological approaches.Systematic analysis of genetic/genomic alterations and further functional studies have led to several important findings,including novel rearrangement hotspots,osteosarcoma-specific LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes,VEGF and Wnt signaling pathway alterations,deletion of the WWOX gene,and amplification of the APEX1 and RUNX2 genes.Importantly,these genetic events associate significantly with pathogenesis,prognosis,progression,and therapeutic activity in osteosarcoma,suggesting their potential impact on improved managements of human osteosarcoma.This international initiative provides opportunities for developing new treatment modalities to conquer osteosarcoma.
文摘目的:研究乳腺癌生成过程中,Wnt家族成员表达的变化规律。方法:收集自发乳腺癌小鼠42只,记录其详细资料。采用基因芯片筛选正常TA2小鼠乳腺组织和自发乳腺癌TA2小鼠乳腺癌组织中的差异表达基因,随后用Real-time PCR进行验证,并检测TA2小鼠乳腺癌形成过程中相关基因表达的变化。结果:TA2自发乳腺癌小鼠平均见瘤年龄为(336.706±85.05)d,平均分娩次数为(3.767±1.79)次。分娩次数最多者为7次,其平均见瘤年龄只有251.5 d。TA2小鼠基因芯片结果发现Wnt家族成员中,Wnt1、Wnt10b、Wnt5a、Wnt5b在正常乳腺组织和乳腺癌组织中表达具有差异。Real time PCR的结果证实了以上结果,并发现Wnt1、Wnt10b、Wnt5a在癌前病变和乳腺癌组织中表达高于正常乳腺组织,而Wnt5b在乳腺癌组织中表达低于正常乳腺组织。结论:Wnt1、Wnt5a、Wmt10b在TA2小鼠乳腺癌生成过程中起促进作用,而Wnt5b的作用可能是抑制小鼠乳腺癌的生成。
