1.Multiregion sequencing reveals intratumor heterogeneity in esophageal squamous cell carcinoma
Wei CAO ; Wei WU ; Ming YAN ; Fu TIAN ; Hansong LIU ; Jinwu WANG ; Quanwu ZHANG ; Yujie LI ; Min LI
Chinese Journal of Oncology 2016;38(9):660-666
Objective To study the intratumor heterogeneity of esophageal squamous cell carcinoma ( ESCC) . Methods We used whole?exome sequencing and array?based comparative genomic hybridization to profile mutations and changes in copy number from 11 regions within 2 cases of ESCC and from the metastatic lymph nodes. Results The numbers of somatic single nuclear polymorphisms ( SNPs ) in 4 regions within the tumors in case 1 and case 2 were 93±17 and 124±28, respectively. The majority of SNPs were non synonymous mutations, synonymous mutations, nonsense mutations and splicing junction mutations. The average indels in the 4 tumor regions of case 1 and case 2 were 40 ± 6 and 51 ± 3, respectively. These small indels mainly occurred in exonic ( frame?shift and non?frame?shift ) , untranslational regions of genes and splicing junction regions. All regions from a tumor exhibitedo bvious heterogeneity, and mutational similarity of all four regions within a tumor was less than 25%. Furthermore, gene copy number alteration ( gain or loss) varied among multiple regions of a tumor, and the similarity of gene copy number was less than 20%. Phylogenetic analysis of the somatic mutation frequency suggests that multiple, genomic heterogeneous clones co?exist within a primary ESCC, and metastatic subclones may evolve from the primary non?metastatic parental clone. These results indicated that a single?region sampling can not reflect the architecture of the genomic landscape of mutations in ESCC tumors. Conclusions Sequence analysis of whole genome exon in multiple regions can provide strong evidence for genomic heterogeneity in esophageal squamous cell carcinoma.
2.Multiregion sequencing reveals intratumor heterogeneity in esophageal squamous cell carcinoma
Wei CAO ; Wei WU ; Ming YAN ; Fu TIAN ; Hansong LIU ; Jinwu WANG ; Quanwu ZHANG ; Yujie LI ; Min LI
Chinese Journal of Oncology 2016;38(9):660-666
Objective To study the intratumor heterogeneity of esophageal squamous cell carcinoma ( ESCC) . Methods We used whole?exome sequencing and array?based comparative genomic hybridization to profile mutations and changes in copy number from 11 regions within 2 cases of ESCC and from the metastatic lymph nodes. Results The numbers of somatic single nuclear polymorphisms ( SNPs ) in 4 regions within the tumors in case 1 and case 2 were 93±17 and 124±28, respectively. The majority of SNPs were non synonymous mutations, synonymous mutations, nonsense mutations and splicing junction mutations. The average indels in the 4 tumor regions of case 1 and case 2 were 40 ± 6 and 51 ± 3, respectively. These small indels mainly occurred in exonic ( frame?shift and non?frame?shift ) , untranslational regions of genes and splicing junction regions. All regions from a tumor exhibitedo bvious heterogeneity, and mutational similarity of all four regions within a tumor was less than 25%. Furthermore, gene copy number alteration ( gain or loss) varied among multiple regions of a tumor, and the similarity of gene copy number was less than 20%. Phylogenetic analysis of the somatic mutation frequency suggests that multiple, genomic heterogeneous clones co?exist within a primary ESCC, and metastatic subclones may evolve from the primary non?metastatic parental clone. These results indicated that a single?region sampling can not reflect the architecture of the genomic landscape of mutations in ESCC tumors. Conclusions Sequence analysis of whole genome exon in multiple regions can provide strong evidence for genomic heterogeneity in esophageal squamous cell carcinoma.
3.Effects of Electroacupuncture on Insulin-like Growth Factor-1, Myostatin and Satellite-cell Proliferation in Rats with Denervated Skeletal Muscle Atrophy
Ruiqi GAO ; Chenglin TANG ; Jing CAO ; Quanwu GUO ; Yi ZHANG ; Yuan TIAN ; Haizhou YUAN
Chinese Journal of Rehabilitation Theory and Practice 2016;22(11):1259-1263
Objective To observe effects and mechanism of electroacupuncture (EA) on denervated skeletal muscle atrophy. Methods Forty-nine male Sprague-Dawley rats were randomly divided into normal group (group A, n=7), natural recovery group (group B, n=21) and EA group (group C, n=21). The groups B and C, established the model of denervated skeletal muscle atrophy by transecting the sciatic nerve of rats, were divided into subgroups of 7 days, 14 days, 21 days postoperation, seven in each subgroup. Electroacupuncture was given to the group C at Zusanli (ST36) and Chengshan (BL57) once a day since 24 hours after modeling. The muscle wet weight ratio of the affected gastrocnemius was determined. Cross-sectional area and fiber diameter of the gastrocnemius were measured with HE staining. The expression of insulin-like growth factor-1 (IGF-1), Myostatin and proliferating cell nuclear antigen (PCNA) protein and gene in the gastrocnemius were detected with Western blotting and RT-PCR. Results The wet weight ratio, cross-sectional area and fiber diameter were less in the groups B and C than in the group A (P<0.001), and they were more in the group C than in the group B (P<0.001). Compared with the group B, the protein and gene of IGF-1, PCNA increased in the group C (P<0.05), while the Myostatin decreased (P<0.05). Conclusion Electroacupuncture can increase the expression of IGF-1 and decrease the expression of Myostatin, to promote the proliferation of satellite cell, which may relate with the prevention of denervated skeletal muscle atrophy.