Owing to a unique set of attributes, human pluripotent stem cells （hPSCs） have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over l...Owing to a unique set of attributes, human pluripotent stem cells （hPSCs） have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure （particularly of chromosomes 1, 12, 17 and 20）, remi- niscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving for- ces behind the genome evolution that may eventually lead to cancerous transformation.展开更多
Context: The incidence of gallbladder cancer is quite low in the US, with an estimate (2013) for new cases of less than 10,000. The rarity suggests a possible shared molecular pathology that might facilitate a greater...Context: The incidence of gallbladder cancer is quite low in the US, with an estimate (2013) for new cases of less than 10,000. The rarity suggests a possible shared molecular pathology that might facilitate a greater understanding of this tumor. Objective: We wished to assess the molecular genetic profile of this tumor, particularly KRAS gene mutations, which are frequent in tumors associated with chronic inflamemation elsewhere within the abdomen. Design: We ascertained 25 cases of gallbladder adenocarcinoma from our pathology department records for 2000-2012. PCR based techniques were used to evaluate the DNA for loss of heterozygosity of the APC and DCC genes;for point mutations in the KRAS gene, codons 12 and 13;for point mutation in the BRAF gene, codon 600;for point mutation in the GNAS gene, codon 201;and for microsatellite instability. Results: Patients included 5 males and 20 females. Approximately three-quarters of cases were associated with gallstones, inflammation and dysplasia. Microsatellite instability and GNAS mutation, both present in just 4% of cases, and BRAF mutation present in no cases, do not appear to be significant parts of carcinogenesis of gallbladder carcinoma. We detected a KRAS gene mutation in only 8% of the cases. Loss of heterozygosity for the APC was detected in 16.7% of informative cases;and for the DCC gene, in 34.8% of informative cases. Conclusions: Many molecular genetic changes frequently seen with tumors arising from other intra-abdominal organs are infrequent in this tumor type. In particular, KRAS mutations were uncommon, in contra-distinction to other malignant tumors developing in the setting of chronic inflammation/infection.展开更多
The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than ha...The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than half of the re-sponders gradually become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnormalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. This article focusedon the role of AR in the progression of prostate cancer. (Asian J Androl 1999 Sep; 1: 81-85)展开更多
Previous studies have shown rapid and extensive genomic However, these studies are based on either a few pre-selected instability associated with early stages of allopolyploidization in wheat. genomic loci or genome-w...Previous studies have shown rapid and extensive genomic However, these studies are based on either a few pre-selected instability associated with early stages of allopolyploidization in wheat. genomic loci or genome-wide analysis of a single plant individual for a given cross combination, thus making the extent and generality of the changes uncertain. To further study the generality and characteristics of allopolyploidization-induced genomic instability in wheat, we investigated genetic and epigenetic changes from a genome-wide perspective （by using the AFLP and MSAP markers） in four sets of newly synthesized allotetraploid wheat lines with various genome constitutions, each containing three randomly chosen individual plants at the same generation. We document that although general chromosomal stability was characteristic of all four sets of allotetraploid wheat lines, genetic and epigenetic changes at the molecular level occurred in all these plants, with both kinds of changes classifiable into two distinct categories, i.e., stochastic and directed. The abundant type of genetic change is loss of parental bands while the prevalent cytosine methylation pattern alteration is hypermethylation at the CHG sites. Our results have extended previous studies regarding allopolyploidization-induced genomic dynamics in wheat by demonstrafing the generality of both genetic and epigenetic changes associated with multiple nascent allotetraploid wheat lines, and providing novel insights into the characteristics of the two kinds of induced genomic instabilities.展开更多
The purpose of the present paper is to study and develop indicators and procedures for the evaluation of genetic structure changes in germplasm conservation due to social and natural environment reasons. Some basic ...The purpose of the present paper is to study and develop indicators and procedures for the evaluation of genetic structure changes in germplasm conservation due to social and natural environment reasons. Some basic concepts in germplasm study were introduced at first. Then, six kinds of indicators for genetic diversity as a measure of genetic potential of a germplasm collection were presented, i.e., numbers of different entities at certain level, evenness of the entity distribution, genetic similarity and genetic distance, genetic variance and genetic coefficient of variation, multivariate genetic variation indices, and coefficient of parentage. It was pointed out that genetic dispersion did not provide a complete concept of genetic diversity if without any information from genetic richness. Based on the above, the indicators for genetic erosion as the genetic structure changes of germplasm conservation due to social reasons, the indicators of genetic vulnerability as the genetic structure changes of germplasm conservation due to environmental stresses, the measurement of genetic drift and genetic shift as the genetic structure changes of germplasm collection during reproduction or seed increase were reviewed and developed. Furthermore, the estimation procedures of the indicators by using molecular markers were suggested. Finally, the case studies on suitable conservation sample size of self-pollinated and open-pollinated populations were given for reference.展开更多
文摘Owing to a unique set of attributes, human pluripotent stem cells （hPSCs） have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure （particularly of chromosomes 1, 12, 17 and 20）, remi- niscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving for- ces behind the genome evolution that may eventually lead to cancerous transformation.
文摘Context: The incidence of gallbladder cancer is quite low in the US, with an estimate (2013) for new cases of less than 10,000. The rarity suggests a possible shared molecular pathology that might facilitate a greater understanding of this tumor. Objective: We wished to assess the molecular genetic profile of this tumor, particularly KRAS gene mutations, which are frequent in tumors associated with chronic inflamemation elsewhere within the abdomen. Design: We ascertained 25 cases of gallbladder adenocarcinoma from our pathology department records for 2000-2012. PCR based techniques were used to evaluate the DNA for loss of heterozygosity of the APC and DCC genes;for point mutations in the KRAS gene, codons 12 and 13;for point mutation in the BRAF gene, codon 600;for point mutation in the GNAS gene, codon 201;and for microsatellite instability. Results: Patients included 5 males and 20 females. Approximately three-quarters of cases were associated with gallstones, inflammation and dysplasia. Microsatellite instability and GNAS mutation, both present in just 4% of cases, and BRAF mutation present in no cases, do not appear to be significant parts of carcinogenesis of gallbladder carcinoma. We detected a KRAS gene mutation in only 8% of the cases. Loss of heterozygosity for the APC was detected in 16.7% of informative cases;and for the DCC gene, in 34.8% of informative cases. Conclusions: Many molecular genetic changes frequently seen with tumors arising from other intra-abdominal organs are infrequent in this tumor type. In particular, KRAS mutations were uncommon, in contra-distinction to other malignant tumors developing in the setting of chronic inflammation/infection.
文摘The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than half of the re-sponders gradually become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnormalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. This article focusedon the role of AR in the progression of prostate cancer. (Asian J Androl 1999 Sep; 1: 81-85)
基金supported by the National Natural Science Foundation of China (No.30870178)
文摘Previous studies have shown rapid and extensive genomic However, these studies are based on either a few pre-selected instability associated with early stages of allopolyploidization in wheat. genomic loci or genome-wide analysis of a single plant individual for a given cross combination, thus making the extent and generality of the changes uncertain. To further study the generality and characteristics of allopolyploidization-induced genomic instability in wheat, we investigated genetic and epigenetic changes from a genome-wide perspective （by using the AFLP and MSAP markers） in four sets of newly synthesized allotetraploid wheat lines with various genome constitutions, each containing three randomly chosen individual plants at the same generation. We document that although general chromosomal stability was characteristic of all four sets of allotetraploid wheat lines, genetic and epigenetic changes at the molecular level occurred in all these plants, with both kinds of changes classifiable into two distinct categories, i.e., stochastic and directed. The abundant type of genetic change is loss of parental bands while the prevalent cytosine methylation pattern alteration is hypermethylation at the CHG sites. Our results have extended previous studies regarding allopolyploidization-induced genomic dynamics in wheat by demonstrafing the generality of both genetic and epigenetic changes associated with multiple nascent allotetraploid wheat lines, and providing novel insights into the characteristics of the two kinds of induced genomic instabilities.
基金supported by the National Natural Science Foundation of China(30270805 and 30490250)Doctorate Foundation of Higher Education(20020307028).
文摘The purpose of the present paper is to study and develop indicators and procedures for the evaluation of genetic structure changes in germplasm conservation due to social and natural environment reasons. Some basic concepts in germplasm study were introduced at first. Then, six kinds of indicators for genetic diversity as a measure of genetic potential of a germplasm collection were presented, i.e., numbers of different entities at certain level, evenness of the entity distribution, genetic similarity and genetic distance, genetic variance and genetic coefficient of variation, multivariate genetic variation indices, and coefficient of parentage. It was pointed out that genetic dispersion did not provide a complete concept of genetic diversity if without any information from genetic richness. Based on the above, the indicators for genetic erosion as the genetic structure changes of germplasm conservation due to social reasons, the indicators of genetic vulnerability as the genetic structure changes of germplasm conservation due to environmental stresses, the measurement of genetic drift and genetic shift as the genetic structure changes of germplasm collection during reproduction or seed increase were reviewed and developed. Furthermore, the estimation procedures of the indicators by using molecular markers were suggested. Finally, the case studies on suitable conservation sample size of self-pollinated and open-pollinated populations were given for reference.
