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Establishment and molecular profiling of a PDX model of a metachronous brain tumor in a patient with constitutional mismatch repair deficiency with biallelic MSH6 variant 认领 引用
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作者 Daniel Antunes Moreno Bruna Minniti Mançano +17 位作者 Mirella Baroni Eric Allison Philot Felipe Antonio de Oliveira Garcia Murilo Bonatelli Flávia Escremim de Paula Iara Viana Vidigal Santana Gustavo Ramos Teixeira Mauricio Yamanari Luciane Sussuchi da Silva AndréEscremim de Paula Augusto Perazzolo Antoniazzi Adrian Willig Xiaobin Xing Zhenyu Xu Lucas Lourenço Carlos Almeida Junior Silvia Aparecida Teixeira Rui Manuel Reis 《Animal Models and Experimental Medicine》 CAS CSCD 2025年第11期1971-1982,共12页
Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachrono... Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors. 展开更多
关键词 Brazil constitutional mismatch repair deficiency exome high-grade glioma medulloblastoma MSH6
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On the Right to the Protection of Personal Data as a Constitutional Right 认领 引用
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作者 戴激涛 LIU Zhao 《The Journal of Human Rights》 2021年第5期851-874,共24页
The right to the protection of personal data is an important human right in the era of big data and a constitutional right based on the national protection obligation and the theory of human dignity,making it of speci... The right to the protection of personal data is an important human right in the era of big data and a constitutional right based on the national protection obligation and the theory of human dignity,making it of special significance for the realization of citizenship in a digital society.It can be seen from an examination of the constitutional texts of various countries in the world that the right to the protection of personal data as a constitutional right has rich normative connotations,and the key legal link to realize this right lies in the national legislature actively fulfilling its obligation to shape and specify the protection of personal data in accordance with the entrustment of the constitutional norms.Given the constitutional principles of fundamental rights protection,i.e.,realizing the constitutional status of the right to the protection of personal data as a basic right by means of institutional guarantees,the legislature should first adhere to the constitutionality principle of data protection legislation.Second,a multi-level data protection legal system centered on the right to the protection of personal data should be established.Finally,the institutional guarantee mechanism for the protection of personal data should be continuously improved through constitutional interpretation. 展开更多
关键词 the right to the protection of personal data constitutional rights institutional guarantees constitutional principles constitutional interpretations
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On the Scope of Constitutional Protection for the Right to Health 认领 引用
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作者 ZHANG Shuaiyu LI Donglin 《The Journal of Human Rights》 2025年第2期395-421,共27页
The understanding of the scope of protection for the right to health should not be limited to fragmented descriptions in departmental laws,such as those focusing on rights,interests,or legal benefits.Instead,it should... The understanding of the scope of protection for the right to health should not be limited to fragmented descriptions in departmental laws,such as those focusing on rights,interests,or legal benefits.Instead,it should be analyzed holistically within the constitutional framework of fundamental rights.From the perspective of defense right function,the right to health addresses physiological harm that progresses through stages of“risk-danger-infringement,”psychological harm that targets inner distress,and minor harm arising from challenges in social adaptation,to clarify the negative defensive obligations of the state to prevent health-related harm.From the perspectives of the beneficiary right function and the objective value order function,the right to health requires a minimum level of constitutional protection and delineating the positive obligations of the state to ensure it through the fulfillment of basic obligations in healthcare and health promotion. 展开更多
关键词 constitution human rights right to health scope of protection state obligations
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Constitutionalism Under Fire: The Constitutional Court of Ukraine as a Guardian of Rights, Justice, and Democracy in Times of War and Transition 认领 引用
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作者 Larysa Zhdankina 《US-China Law Review》 2025年第5期205-217,共13页
During a full-scale destructive war in Ukraine,constitutional control,as an element of the state system of legal protection of fundamental values and guarantees of human rights,has embodied the people’s will to estab... During a full-scale destructive war in Ukraine,constitutional control,as an element of the state system of legal protection of fundamental values and guarantees of human rights,has embodied the people’s will to establish peace,freedom,democracy,respect for human dignity,and protection of human rights.The Constitutional Court of Ukraine,as a state body with unique powers to maintain the balance of power,plays a fundamental role in ensuring that legislation aligns with constitutional principles and human rights standards during this difficult period.Since gaining independence in 1991,Ukraine has faced two simultaneous transitions:overcoming its post-Soviet legacy that has flooded all spheres of public and state life and defending against Russian military aggression for over 11 years.This paper explores the role of constitutional review in Ukraine during its full-scale war,highlighting its significance as part of the state’s legal framework for protecting human rights and core values.It examines the contribution of the Constitutional Court of Ukraine to restoring human rights and improving constitutional oversight,especially during the adoption and amendment of laws.Specific decisions of the Constitutional Court of Ukraine showcase its ability to address remnants of Ukraine’s colonial Soviet past and its potential to shape institutional reforms that may become integral to Ukraine’s transitional justice system in the post-war era.While the Constitutional Court is not a legislator,its decisions provide a crucial finality to the law-making process,positioning it as a key actor in Ukraine’s transitional justice efforts. 展开更多
关键词 constitutional control transitional justice post-Soviet legacy human rights protection post-war reconstruction
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宪法上的Civil Rights是公民权利吗?——解读constitutional civil right 认领 引用 被引量：9
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作者 郑贤君 《首都师范大学学报（社会科学版）》 2004年第4期47-56,共10页
作为西方法律文化的产物 ,constitutionalcivilrights有其独特的自然法背景。本文通过对西方法律思想史、宪法史和美国最高法院司法实务见解的梳理与综合分析 ,认为将constitutionalcivilrights译为“公民权利”属于误读 ,它混淆了依据... 作为西方法律文化的产物 ,constitutionalcivilrights有其独特的自然法背景。本文通过对西方法律思想史、宪法史和美国最高法院司法实务见解的梳理与综合分析 ,认为将constitutionalcivilrights译为“公民权利”属于误读 ,它混淆了依据人的属性和依据公民资格而获得的权利之间的道德区别。应将其译为“私人权利” ,明确这一权利体系的前国家与超国家特征 ,使其区别于实证法律传统之下个人依赖作为政治社会成员资格所享有的公民权利 ,并区分宪法权利与民事权利之间的差异。在法官的解释下 ,constitutionalcivilrights还呈现出开放特性 ,是一个能够感应时代变化的、发展的权利体系。 展开更多
关键词 Constitutional Civil Rights 自然权利 个人权利 私人权利 宪法权利
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Constitutional Environmental Rights: An Investigation and Analysis Based on Constitutional Texts of All Countries 认领 引用 被引量：2
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作者 范进学 HAN Feng 《The Journal of Human Rights》 2017年第5期476-492,共17页
Although the academic community still has some theoretical divergences on whether environmental rights should be a basic human right or a basic constitutional one, there are an increasing number of countries including... Although the academic community still has some theoretical divergences on whether environmental rights should be a basic human right or a basic constitutional one, there are an increasing number of countries including this right in their constitution. Based on the constitutions in 193 countries, this paper aims to examine the fundamental situation of incorporating environmental rights into a constitution. It has been concluded that environmental protection as a right is written into a constitution in three aspects, namely, as a constitutional right, a civic duty, and a national policy, principle or social goal. Through summarizing these, this paper argues that including environmental rights in a country’s constitution is the means by which all citizens shall enjoy a good, healthy, sustainable and harmonious environment suitable for their development, have timely and comprehensive access to reliable information about environment, participate in making public decisions related to the environment, and ask for legal remedies and compensation for any infringement on their environmental rights, or injury or damage to their environmental property. But even after environmental rights are incorporated into a constitution, there may be theoretical and practical difficulties in their implementation. 展开更多
关键词 constitutional environmental rights basic duty national policy right relief
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CONSTITUTIONAL DIAGRAM OF Fe-Mn-C ALLOYS AFTER SOLUTION TREATMENT AT 1000℃ 认领 引用
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作者 LI Shaoxiong HE Zhenming ZHAO Yuguang ZHAO Yuqian SHI Zhongliang Jilin University of Technology,Changchun,China 《Acta Metallurgica Sinica(English Letters)》 CAS 1992年第8期94-98,共5页
On the basis of experimental results of 76 points of composition and previous relevant conclu- sions,a relatively complete constitutional diagram of solid solution treating Fe-Mn-C sys- tem alloy at 1000℃ has been co... On the basis of experimental results of 76 points of composition and previous relevant conclu- sions,a relatively complete constitutional diagram of solid solution treating Fe-Mn-C sys- tem alloy at 1000℃ has been constructed with austenite zones of different stabilities.The chemical composition range and structure change of steels with various Mn have also been discussed.Thus,the reasonable selection of composition and structure may be available for the manganese steel with commercial purposes. 展开更多
关键词 constitutional diagram Fe-Mn-C alloy austenite
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Constitutional Analysis of the Personality Theory of Civil Law 认领 引用
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作者 刘志刚 LU Dongmin 《The Journal of Human Rights》 2019年第4期471-494,共24页
The word"personality"has various connotations,which essentially reflect people’s thoughts on personality in different periods.The transformation of personality in a civil aspect to the personality on the co... The word"personality"has various connotations,which essentially reflect people’s thoughts on personality in different periods.The transformation of personality in a civil aspect to the personality on the constitution aspect has negative effect on the personality system of the civil,which is of great value to develop the civil personality rights system in order to facilitate the connection between the civil law,the constitution and the public law.The capacity for rights not only separates the relative independent personality rights of civil law from the personality system of Roman law,but also promotes the emergence of the constitutional personality rights and its return in the field of civil law.The nature and orientation of personality rights in civil law has an important influence on civil legislation.There are three ways to realize the constitutional rights of personality in our civil law:civil legislation,constitutional interpretation and general personality rights. 展开更多
关键词 personality right capacity civil personality right constitutional personality right constitutional analysis
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Rethinking on constitutional application 认领 引用
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作者 王德志 《US-China Law Review》 2009年第10期12-25,35,共14页
The constitutional application is a type of special activity that the state organs deal with the specific cases or disputes according to legitimate authority and legal procedure. The following activities don＇t belong... The constitutional application is a type of special activity that the state organs deal with the specific cases or disputes according to legitimate authority and legal procedure. The following activities don＇t belong to the constitutional application, such as legislation and law revision of the People＇s Congress and its standing committee; working out administrative measures and regulations of the State Council; the activities of issuing the decision and order. Whether based on the power＇s origin or the substantive law basis for trying a case of the People Court, the ＂law＂ in the article 126 of our constitution is a law of wide meaning that includes constitution. The pluralistic and multistage legislative system leaves room for the People Court＇s constitutional review, which is aiming at the normative documents made by the appurtenant law-making organs. 展开更多
关键词 constitutional application concept subject range
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Constitutional Nature of Personality Rights and Its Manifestation in Civil Law 认领 引用
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作者 陈斯彬 《The Journal of Human Rights》 2023年第4期804-825,共22页
The formation of personality comes from people’s choices and pursuit of self-realization,which is influenced by objective factors but not determined by them,so personality does not belong to the domain of objectivity... The formation of personality comes from people’s choices and pursuit of self-realization,which is influenced by objective factors but not determined by them,so personality does not belong to the domain of objectivity.The concept of general personality rights in the German Constitution was initially premised on the objective determinability in the field of personality,but in constitutional jurisprudence,it gradually shifted to something with individual autonomy as the core and personal self-realization as the goal,and the scope of relevant rights expanded accordingly,so that they could not be clearly distinguished from general freedom of action and thus became the general principle of constitutional rights.The protection of constitutional personality rights in the United States and Japan can also confirm this process,providing evidence for the constitutional nature of personality rights.Deeper research shows that constitutional personality rights actually manifest the highest value of modern constitutions—human dignity.In contrast,the theoretical justification of personality rights in civil law just lies in the objectivity and defensive nature of personality elements. 展开更多
关键词 general personality rights constitutional personality rights self-realization self-determination human dignity
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High-temperature creep constitutional model of Q460E steel and effect of creep on bulging deformation of continuous casting slab 认领 引用 被引量：2
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作者 Long Guo Yun-huan Sui Xing-zhong Zhang 《Journal of Iron and Steel Research International》 SCIE EI CAS CSCD 2018年第11期1123-1130,共8页
Mechanical properties and creep behavior of Q460E continuous casting slab were studied by means of uniaxial tensile tests on a Gleeble-3800 thermomechanical simulator from 1000 to 1100 ℃.The high-temperature creep co... Mechanical properties and creep behavior of Q460E continuous casting slab were studied by means of uniaxial tensile tests on a Gleeble-3800 thermomechanical simulator from 1000 to 1100 ℃.The high-temperature creep constitutional equation was derived based on experimental data.The parameters in the equation were calculated by using the regression analysis inverse-estimation method.The experimental curves in the primary and secondary creep stages are fitted well.A three-dimensional elastic-plastic and creep finite element model was proposed in order to investigate the bulging deformation of slab and the bulging deformation at the beginning position of bending segment on the slab continuous casting machine was computed accurately.The results indicate that the maximum bulging deformation appears at the geometric center of the slab.The maximum value of the bulging deformation obtained by the elastic-plastic analysis is 1.301 ram.Consideririg the creep effect,the deformation increases to 1.827 mm which is about 1.4 times the value obtained by the elastic-plastic analysis.The calculation of buleing deformation usin2 the elastic-plastic creed model is more reliable and/iccurate. 展开更多
关键词 Steel mechanical property High temperature creep behavior Creep constitutional equation Bulging deformation Steel continuous casting
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Rim-differentiation vs. mixture of constitutional isomers: A binding study between pillar[5]arene-based glycoclusters and lectins from pathogenic bacteria 认领 引用 被引量：1
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作者 Zhiping Liu Fanny Demontrond +3 位作者 Anne Imberty Andrew C.-H.Sue Sébastien Vidal Hongxia Zhao 《Chinese Chemical Letters》 SCIE CAS CSCD 2023年第2期214-218,共5页
Macrocycle-based glycoclusters, on account of their promising anti-adhesive properties against bacteria,are potential therapeutic alternatives to classic antibiotics through the much less explored anti-adhesive strate... Macrocycle-based glycoclusters, on account of their promising anti-adhesive properties against bacteria,are potential therapeutic alternatives to classic antibiotics through the much less explored anti-adhesive strategy. In this study, a series of constitutionally-pure pentavalent glycoclusters was prepared by conjugating assorted azido-carbohydrates onto a penta-propargyl rim-differentiated pillar[5]arene(RD-P[5])scaffold through Cu(I)-catalyzed azide–alkyne cycloaddition “click” reactions. Their binding towards therapeutically relevant bacterial lectins, such as Lec A and Lec B from Pseudomonas aeruginosa and concanavalin A(Con A), were evaluated subsequently by isothermal titration calorimetric studies. Most of these isomerfree RD-P[5] pentavalent glycoclusters, except the fucosylated ones, display good affinities to lectins.Nonetheless, the dissociation constants observed are similar to those displayed by an analogous pentavalent glycocluster consisting of four P[5] constitutional isomers, in which the RD-P[5] component merely accounts for 7% in the mixture. Our results revealed that high constitutional purity is not essential for achieving effective multivalent interactions between P[5]-based glycoclusters and lectins, presumably as a result of the conformationally labile nature of the P[5] scaffold. This information provides valuable design principles for low-cost and facile syntheses of glycosylated P[5]s for biomedical applications. 展开更多
关键词 Glycocluster Lectin Pillararene Multivalency Constitutional purity
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The Constitutional Analysis of Human Rights Legislative Protection 认领 引用
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作者 刘志刚 《The Journal of Human Rights》 2015年第3期286-297,共12页
The paths for applying the international human rights conventions in China should be recognized as follows: On the premise of respecting the Constitution of China, systematic human rights which could coordinate the re... The paths for applying the international human rights conventions in China should be recognized as follows: On the premise of respecting the Constitution of China, systematic human rights which could coordinate the relationship between the Constitution of China and international human rights conventions. The source of the human rights legislation obligations of the legislative organs of China is the Constitution of China, not the international human rights conventions. The legislature should understand and grasp the main contents of the human rights legislation obligations of the legislature according to Paragraph 3 of Article 33 of the Constitution while the interpretation of this clause must be based on the relevant provisions of the international human rights conventions. Human rights legislative obligations of the legislature can be classified into two types: legislative protecting obligations and legislative relief obligations of human rights. The NPC and its Standing Committee should be structurally responsible for the human rights legislation obligation, and the State Council and other organs of the State not for the legislation protection of human rights. A special human rights law should be enacted by the NPC. 展开更多
关键词 international human rights conventions legislative protection human rights constitutional analysis
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Constitutional/Conditional Acupuncture 认领 引用
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作者 Peter Eckman 《Chinese Medicine and Culture》 2018年第1期46-48,共3页
A new style of acupuncture,named constitutional/conditional acupuncture(CCA),based on traditional Asian medical practices,was revealed in Kunming in 2017.This method is primarily based on pulse diagnosis,as developed ... A new style of acupuncture,named constitutional/conditional acupuncture(CCA),based on traditional Asian medical practices,was revealed in Kunming in 2017.This method is primarily based on pulse diagnosis,as developed in China,Korea,and India.The basic methods of CCA are briefly described,and a few case results from the 3‑day Kunming workshop are presented to reveal the efficacy of CCA. 展开更多
关键词 Ayurveda condition constitution Korean acupuncture Mai Jing Nan Jing Nei Jing pulse diagnosis renying cunkou diagnosis sasang constitutional medicine traditional Chinese medicine Yi Jing
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Principles,Standards,and Applicability of Constitutional Interpretation of Basic Rights 认领 引用 被引量：1
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作者 DONG Jian 《The Journal of Human Rights》 2024年第5期1054-1075,共22页
For departmental legal norms concerning citizens’basic rights,when multiple interpretations are possible based on individual case circumstances,interpreters representing public authority need to apply the method of c... For departmental legal norms concerning citizens’basic rights,when multiple interpretations are possible based on individual case circumstances,interpreters representing public authority need to apply the method of constitutional interpretation to screen out the interpretation conclusions that do not violate the Constitution.This means selecting interpretations at the constitutional level that do not overly restrict citizens’basic rights and understanding the specific connotations of legal norms with the principle of“not infringing on citizens’basic rights.”The Constitution,as a framework order,does not require interpreters to choose the most constitutionally aligned interpretation among various constitutional interpretations.If a legal norm does not have a constitutional interpretation conclusion in an individual case circumstance,it indicates that the application of that norm in the case is unconstitutional,and the interpreter should avoid applying the legal norm in that case.Regarding judgment standards,interpreters should apply the principle of proportionality to determine whether each legal interpretation conclusion concerning basic rights-related legal norms complies with the Constitution.Out of respect for the legislature,the application of the sub-principles of pro-portionality should consider the boundaries of interpretative actions. 展开更多
关键词 basic rights constitutional interpretation constitu-tionally aligned interpretation principle of proportionality
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The Connotations of the Constitutional Clause on Human Rights Protection From the Perspective of Foreign-related Rule of Law 认领 引用 被引量：1
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作者 ZHAI Han 《The Journal of Human Rights》 2024年第3期548-566,共19页
The inclusion of the human rights clause in the Chi-nese Constitution is the core normative manifestation of the constitu-tionalization of human rights,and points to the relationship between international law and the ... The inclusion of the human rights clause in the Chi-nese Constitution is the core normative manifestation of the constitu-tionalization of human rights,and points to the relationship between international law and the Constitution in the sense of positive law.The inclusion of the human rights clauses in the Chinese Constitution itself is an inherent part of the development of China’s socialist constitution,and socialism has already contributed valuable concepts and practices of human rights protection to the modern world in its early stage.The constitutionalization of human rights protection does not necessarily lead to the superiority of international law over the constitutional order of a country,but rather to the convergence of international law and domestic law through the constitutional order.The relevant rules of international law will be effective only when they are transformed into domestic law through the Constitution and the human rights clause in the Constitution.Correspondingly,the domestic legal order is brought into line with the international legal order through the Con-stitution and its human rights clause.Behind the system of fundamen-tal rights in the constitutional order is the value foundation of the en-tire legal system.The advancement of foreign-related rule of law has brought new opportunities for China’s judicial practice to further pro-mote the protection of human rights.In the future,we should further integrate the human rights values embedded in socialism into China’s constitutional practice,enhance human rights protection around the country,and take a more active part in global human rights gover-nance. 展开更多
关键词 human rights clause foreign-related rule of law socialist constitution constitutionalization of human rights
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On the Constitutional Prescription to “Respect and Ensure Human Rights” 认领 引用
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作者 SUN PINGHUA 《The Journal of Human Rights》 2013年第1期17-21,共5页
From a historical perspective, the 1982 Constitution was the best one since the founding of the People＇s Republic ofChina （PRC） in 1949.1 With the passage of time and increasing demands from society, China experien... From a historical perspective, the 1982 Constitution was the best one since the founding of the People＇s Republic ofChina （PRC） in 1949.1 With the passage of time and increasing demands from society, China experienced the new sit- uation of modernization, which brought about new conditions or problems in the process of reform and opening up. As a result, the content of the Constitution could not always comply with real conditions. Therefore, the national leg- islature adopted four amendments to the Constitution in 1988, 展开更多
关键词 Respect and Ensure Human Rights On the Constitutional Prescription to CPC
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Japan's Political Situation vs.the Constitutional Amendment 认领 引用
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作者 Hu Lingyuan Kou Jianqiao 《Contemporary International Relations》 2020年第1期110-131,共22页
The year 2019 marks the seventh anniversary of Shinzo Abe's return to office,alongside the administration's obsession with Constitutional amendment.During the 25th House of Councillors selection in July,Prime ... The year 2019 marks the seventh anniversary of Shinzo Abe's return to office,alongside the administration's obsession with Constitutional amendment.During the 25th House of Councillors selection in July,Prime Minister Abe changed the rules applied for the four national elections in 2012,wrote the Self-Defense Forces into the Constitution and the Liberal Democratic Party(LDP)convention,and deliberately made the amendment a focal point of controversy in his election campaign.However,when the results of the election came out,the pro-amendment forces,with the LDP at their core,didn't reach the two-thirds majority threshold required for Constitutional revision.Going forwards,the Abe-led Liberal Democratic Party will strive to consolidate Constitutional amendment forces in the National Diet,hoping to cross the majority threshold,and at the same time to coerce opposition parties to comply with passing LDP draft revisions to the Constitution in the National Diet as soon as possible,in order to submit these to national referendum.In the meantime,preparatory works for this referendum are being carried out through the use of political resources to mobilize public support.Whether Abe can reach the political objective of Constitutional amendment during his current term of office and how the Constitutional issue in Japan will play out is sure to attract global attention. 展开更多
关键词 Japan politics House of Councillors election Constitutional Amendment in explicit text trend of Constitutional Amendment
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Predominance of constitutional chromosomal rearrangements in human chromosomal fragile sites 认领 引用
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作者 Ines J.Sequeira Joao T.Mexia +6 位作者 Joao Santiago Rita Mamede Elisa Silva Jorge Santos Daniel Faria Jose Rueff Aldina Bras 《Open Journal of Genetics》 CAS 2013年第2期8-13,共6页
Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECIPHER (Database... Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECIPHER (Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources). We mapped fragile sites to chromosomal bands and divided the 23 chromosomes into fragile and non-fragile sites. The frequency of rearrangements at the chromosomal location of clones found to be deleted or duplicated in the array/CGH analysis, provided by DECIPHER, was compared in Chromosomal Fragile Sites vs. non-Fragile Sites of the human genome. The POSSUM Web was used to complement this study. The results indicated 1) a predominance of rearrangements in CFSs, 2) the absence of statistically significant difference between the frequency of rearrangements in common CFSs vs. rare CFSs, 3) a predominance of deletions over duplications in CFSs. These results on constitutional chromosomal rearrangements are evocative of the findings previously reported by others relatively to cancer supporting the current line of evidence and suggesting that a common mechanism can underlie the generation of constitutional and somatic rearrangements. The combination of insights obtained from our results and their interrelationships can indicate strategies by which the mechanisms can be targeted with preventive medical interventions. 展开更多
关键词 Chromosomal Fragile Sites Constitutional Chromosomal Rearrangements Databases
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Constitutional Mismatch Repair-Deficiency Syndrome Is a Rare Cause of Cancer Even in a Highly Consanguineous Population 认领 引用
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作者 Rong Bu Abdul K. Siraj +3 位作者 Prashant Bavi Asim Belgaumi Shahab Uddin Fowzan S. Alkuraya 《Journal of Cancer Therapy》 2013年第5期996-1004,共9页
Biallelic germline mutations in the mismatch repair genes, including MLH1, MSH2, MSH6 or PMS2, lead to a recessive constitutional mismatch repair-deficiency (CMMR-D) syndrome characterized by early onset malignancies ... Biallelic germline mutations in the mismatch repair genes, including MLH1, MSH2, MSH6 or PMS2, lead to a recessive constitutional mismatch repair-deficiency (CMMR-D) syndrome characterized by early onset malignancies in children and young adults. Because consanguinity unmasks autosomal recessive disorders, we hypothesized that the frequency of CMMR-D is inflated in the highly consanguineous population of Saudi Arabia. In this study, 371 pediatric and young adult?patient samples from Saudi Arabia that cover the tumor spectrum of CMMR-D syndrome were analyzed for biallelic germline mutations in the MLH1, MSH2, MSH6 and PMS2 with the use of direct genomic sequencing. However, none of the 371 patients involved in the study was found to have biallelic pathological mutations of MLH1, MSH2, MSH6 or PMS2. This result indicates that CMMR-D is exceptionally rare among pediatric cancer patients and adult early onset cancer patients, even in the highly consanguineous Saudi population. Our findings suggest that larger cohorts will be needed, particularly in outbred populations, to determine the frequency of CMMR-D and that routine screening for this syndrome among cancer patients is not warranted. 展开更多
关键词 Constitutional Mismatch Repair-Deficiency (CMMR-D) Lynch Syndrome (LS) MLH1 MSH2 MSH6 and PMS2 Biallelic Germline Mutations
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