The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene...The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.展开更多
<strong>Background</strong><span style="font-family:Verdana;"><strong>:</strong></span><b><span style="font-family:""> </span></b>&l...<strong>Background</strong><span style="font-family:Verdana;"><strong>:</strong></span><b><span style="font-family:""> </span></b><span style="font-family:""><span style="font-family:Verdana;">Malignant granular cell tumor (GCT) is extremely rare. Malignant GCT with EP300 gene mutation in the bladder has not been reported in the literature. </span><b><span style="font-family:Verdana;">Case Presentation</span></b></span><b><span style="font-family:Verdana;">:</span></b><span style="font-family:""><span style="font-family:Verdana;"> We report a special case of 45-year-old female with malignant GCT of the bladder. Pathological examination showed that the mass was 11 × 11 × 4.5 cm in size, involved in the bladder’s posterior wall. Under the microscope, the tumor cells were arranged in the shape of a nest or cord to infiltrate the bladder’s wall. The tumor cells were pleomorphic, red-stained granular within the cytoplasm, with increased nuclear/cyto</span><span style="font-family:Verdana;">plasmic ratio, vacuolar nuclei, and obvious nucleoli. The tumor cells were</span> <span style="font-family:Verdana;">showed obvious nuclear atypia, and the mitosis was more than 5/50HPF. </span><span style="font-family:Verdana;">Coagulative necrosis was widely showed within the tumor. Immunohistochemi</span><span><span style="font-family:Verdana;">stry (IHC) showed that S-100, NSE, CD68, CR, </span><i><span style="font-family:Verdana;">α</span></i><span style="font-family:Verdana;">-AT, and TFE-3 were</span></span><span style="font-family:Verdana;"> strongly </span><span style="font-family:Verdana;">positive, and the Ki-67 proliferation index was around 15%. The</span><span style="font-family:Verdana;"> next-genera</span><span style="font-family:Verdana;">tion high throughput sequencing indicated that EP300 gene was missense</span><span style="font-family:Verdana;"> mutated (c.457A > G) with 33% mutation abundance, and genes of DPYD (c.1627A > G), ERCC1 (c.354T > C), NQO1 (c.559C > T), TPMT (c.719A > G) and XRCC1 (c.1196A > G) were polymorphic mutated. The patient died after three months of the second surgical treatment. </span><b><span style="font-family:Verdana;">Conclusions</span></b></span><b><span style="font-family:Verdana;">:</span></b><b><span style="font-family:""> </span></b><span style="font-family:Verdana;">We report for the first time a primary bladder malignant GCM accompanied by mutations in special driving genes such as EP300. We also conducted a comprehensive literature review and an in-depth discussion.</span>展开更多
Objective: The results of a previous study showed that a clear dysregulation was evident in the global gene expression of the BCL11A-suppressed B-lymphoma cells. In this study, the bone morphogenetic protein receptor,...Objective: The results of a previous study showed that a clear dysregulation was evident in the global gene expression of the BCL11A-suppressed B-lymphoma cells. In this study, the bone morphogenetic protein receptor, type II(BMPR2), E1 A binding protein p300(EP300), transforming growth factor-β2(TGFβ2), and tumor necrosis factor, and alpha-induced protein 3(TNFAIP3) gene expression patterns in B-cell malignancies were studied. Methods: The relative expression levels of BMPR2, EP300, TGFβ2, and TNFAIP3 mRNA in B-lymphoma cell lines, myeloid cell lines, as well as in cells from healthy volunteers, were determined by real-time quantitative reverse transcriptpolymerase chain reaction(qRT-PCR) with SYBR Green Dye. Glyceraldehyde-3-phosphate dehydrogenase(GAPDH) was used as reference. Results: The expression level of TGFβ2 mRNA in B-lymphoma cell lines was significantly higher than those in the cells from the healthy control(P<0.05). However, the expression level of TNFAIP3 mRNA in B-malignant cells was significantly lower than that of the healthy control(P<0.05). The expression levels of BMPR2 and EP300 mRNA showed no significant difference between B-malignant cell lines and the healthy group(P>0.05). In B-lymphoma cell lines, correlation analyses revealed that the expression of BMPR2 and TNFAIP3(r=0.882, P=0.04) had significant positive relation. The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in cell lines from myeloid leukemia were significantly lower than those in the cells from the healthy control(P<0.05). The expression levels of TGFβ2 mRNA showed no significant difference between myeloid leukemia cell lines and the healthy control or B-malignant cell lines(P>0.05). The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in B-lymphoma cells were significantly higher than those of the myeloid leukemia cells(P<0.05).Conclusion: Different expression patterns of BMPR2, EP300, TGFβ2, and TNFAIP3 genes in B-lymphoma cells exist.展开更多
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou,31501013 to HZ,and 31360032 to CC)+2 种基金the National 973 program(2012CB518202 to TW)the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04)the Zhufeng Scholar Program of Tibetan University
文摘The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 （histone acetyltransferase p300）, we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide （NO） concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.
文摘<strong>Background</strong><span style="font-family:Verdana;"><strong>:</strong></span><b><span style="font-family:""> </span></b><span style="font-family:""><span style="font-family:Verdana;">Malignant granular cell tumor (GCT) is extremely rare. Malignant GCT with EP300 gene mutation in the bladder has not been reported in the literature. </span><b><span style="font-family:Verdana;">Case Presentation</span></b></span><b><span style="font-family:Verdana;">:</span></b><span style="font-family:""><span style="font-family:Verdana;"> We report a special case of 45-year-old female with malignant GCT of the bladder. Pathological examination showed that the mass was 11 × 11 × 4.5 cm in size, involved in the bladder’s posterior wall. Under the microscope, the tumor cells were arranged in the shape of a nest or cord to infiltrate the bladder’s wall. The tumor cells were pleomorphic, red-stained granular within the cytoplasm, with increased nuclear/cyto</span><span style="font-family:Verdana;">plasmic ratio, vacuolar nuclei, and obvious nucleoli. The tumor cells were</span> <span style="font-family:Verdana;">showed obvious nuclear atypia, and the mitosis was more than 5/50HPF. </span><span style="font-family:Verdana;">Coagulative necrosis was widely showed within the tumor. Immunohistochemi</span><span><span style="font-family:Verdana;">stry (IHC) showed that S-100, NSE, CD68, CR, </span><i><span style="font-family:Verdana;">α</span></i><span style="font-family:Verdana;">-AT, and TFE-3 were</span></span><span style="font-family:Verdana;"> strongly </span><span style="font-family:Verdana;">positive, and the Ki-67 proliferation index was around 15%. The</span><span style="font-family:Verdana;"> next-genera</span><span style="font-family:Verdana;">tion high throughput sequencing indicated that EP300 gene was missense</span><span style="font-family:Verdana;"> mutated (c.457A > G) with 33% mutation abundance, and genes of DPYD (c.1627A > G), ERCC1 (c.354T > C), NQO1 (c.559C > T), TPMT (c.719A > G) and XRCC1 (c.1196A > G) were polymorphic mutated. The patient died after three months of the second surgical treatment. </span><b><span style="font-family:Verdana;">Conclusions</span></b></span><b><span style="font-family:Verdana;">:</span></b><b><span style="font-family:""> </span></b><span style="font-family:Verdana;">We report for the first time a primary bladder malignant GCM accompanied by mutations in special driving genes such as EP300. We also conducted a comprehensive literature review and an in-depth discussion.</span>
基金supported by the Guangdong Province Key Foundation of Science and Technology Program (Grant No.2009B0507000029)the Guangdong Province Science and Technology Program (Grant No.2012B031800474)a grant from the Overseas Chinese Affairs Office of the State Council Key Discipline Construction Fund (Grant No.51205002)
文摘Objective: The results of a previous study showed that a clear dysregulation was evident in the global gene expression of the BCL11A-suppressed B-lymphoma cells. In this study, the bone morphogenetic protein receptor, type II(BMPR2), E1 A binding protein p300(EP300), transforming growth factor-β2(TGFβ2), and tumor necrosis factor, and alpha-induced protein 3(TNFAIP3) gene expression patterns in B-cell malignancies were studied. Methods: The relative expression levels of BMPR2, EP300, TGFβ2, and TNFAIP3 mRNA in B-lymphoma cell lines, myeloid cell lines, as well as in cells from healthy volunteers, were determined by real-time quantitative reverse transcriptpolymerase chain reaction(qRT-PCR) with SYBR Green Dye. Glyceraldehyde-3-phosphate dehydrogenase(GAPDH) was used as reference. Results: The expression level of TGFβ2 mRNA in B-lymphoma cell lines was significantly higher than those in the cells from the healthy control(P<0.05). However, the expression level of TNFAIP3 mRNA in B-malignant cells was significantly lower than that of the healthy control(P<0.05). The expression levels of BMPR2 and EP300 mRNA showed no significant difference between B-malignant cell lines and the healthy group(P>0.05). In B-lymphoma cell lines, correlation analyses revealed that the expression of BMPR2 and TNFAIP3(r=0.882, P=0.04) had significant positive relation. The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in cell lines from myeloid leukemia were significantly lower than those in the cells from the healthy control(P<0.05). The expression levels of TGFβ2 mRNA showed no significant difference between myeloid leukemia cell lines and the healthy control or B-malignant cell lines(P>0.05). The expression levels of BMPR2, EP300, and TNFAIP3 mRNA in B-lymphoma cells were significantly higher than those of the myeloid leukemia cells(P<0.05).Conclusion: Different expression patterns of BMPR2, EP300, TGFβ2, and TNFAIP3 genes in B-lymphoma cells exist.
