恶性卵巢肿瘤患者体细胞染色体不稳定性及脆性部位的研究

恶性卵巢肿瘤患者体细胞染色体不稳定性及脆性部位的研究王淑珍，包淑和，康过秦染色体的不稳定性与肿瘤发生的关系及染色体脆性部位同癌基因，癌特异性断点的相关关系已成为医学遗传学研究的重要课题，我们通过时１５例恶性卵巢肿瘤患者淋巴细胞染色体结构畸变（ＣＡＲ）...     

两对鼻咽癌患者及其孪生姐妹的染色体脆性部位分析

本文分析了两例鼻咽癌患者及其同卵孪生姐妹的染色体脆性部位，结果显示：两例鼻咽癌患者及其孪生姐妹的染色体脆性部位表达率较正常人群高，而且臆性部位3p14检出率远远超出正常人群．提示了她们具有染色体不稳定性的遗传基础，3pl4可能在鼻咽癌的发生中起一定作用．为进一步研究遗传因素和3p14与鼻咽癌的发生关系，对这孪生姐妹作长期观察和特殊随访是十分必要的。     

染色体不稳定性与乳腺癌发病的关系

目的通过对乳腺癌患者外周血淋巴细胞染色体不稳定性的研究,来探讨乳腺癌患者外周血淋巴细胞中染色体畸变率（Chromosom alaberration,CAR）、染色体脆性部位（frahglg site）、姐妹染色单体交换（sister chromati dexchanges,SCE）、微核发生率（micronuclei,MN）及核仁组织形成区（Nucieolus organizer regioil,NOR）的相关性。方法对84例乳腺癌患者和110例正常人进行外周血染色体培养,常规收获细胞、制片,观察正常人和乳腺癌患者的染色体畸变率、染色体脆性部位、姐妹染色单体交换率、微核发生率、核仁组织形成区,并比较结果。结果①84例乳腺癌患者染色体结构畸变出现较多的的是i、3、5、6、10、11、17。②CAR、SCE频率、MN、AgNOR分别为11.07％、12.76±1.73、2．42±0．68‰、42.74％。③乳腺癌CAR、fra、SCE频率、MN、AgNOR各指标间呈正相关。结论乳腺癌患者外周血淋巴细胞染色体存在着数目及结构畸变,染色体畸变是导致乳腺癌发生的重要原因。肿瘤患者淋巴细胞染色体不稳定性的发生是其必然的表现,通过染色体不稳定性检测有助于发现高危患者。     

智力低下儿童外周血淋巴细胞染色体畸变及脆性部位表达的研究

采用低叶酸含量的Tc199培养基和阿糖胞苷处理，观察10例智力低下儿童及10例智力正常儿童外周血淋巴细胞染色体畸变及脆性部位表达．结果表明，智力低下儿童诱发及自发染色体畸变率及脆性部位表达率均高于正常对照组．经诱发，患者脆性部位3p14，7q32，4q31，1p32，10q22，14q23等出现频率较多。     

脆性X染色体表达的遗传控制

脆性X染色体的脆性部位是Xq27,它与X连锁智力低下有关。脆性部位的细胞表达率有一定的变异,细胞环境的改变和遗传因素都可影响脆性部位表达的变异。本文报告83例有脆性X染色体的比利时家系中,所有男性的脆性X的细胞比例及与遗传因素的相关性。     

大肠癌患者及家族成员染色体脆性部位和癌基因位点的研究

大肠癌患者及家族成员染色体脆性部位和癌基因位点的研究李明烈，程俊，莫善兢近年来，有关染色体不稳定性与癌变机理之间相关性研究、其中尤以肿瘤患者及其易感个体的染色体脆性部位的存在正引起人们极大关注。迄今为止，国内外有关大肠癌及其易感个体的脆性部位研究的报...     

习惯性流产夫妇染色体脆性部位观察

习惯性流产夫妇染色体异常率一般在10%以下，而自然流产的胚胎染色体异常发生率为50～60%，这可能与亲代染色体不稳定性增高，而诱发生殖细胞及胚胎染色体异常有关。本文对40对习惯性流产夫妇和13对生育正常夫妇的外周血淋巴细胞染色体脆性部位进行对照分析，结果如下。     

CD13的表达水平与骨肉瘤患者的临床病理特征的相关性研究

目的观察CD13(氨肽酶N)在骨肉瘤组织中的表达情况,并探索其与骨肉瘤患者临床病理特征的相关性。方法以80例骨肉瘤及其癌旁组织和40例良性骨癌组织作为研究对象,用免疫组织化学染色的方法检测各样本CD13的蛋白表达水平,分析CD13表达水平与各患者临床病理特征的相关性。同时选取收集的32例骨肉瘤组织,以荧光定量PCR的方法测定其CD13 m RNA相对表达水平,并与癌旁组织比较。结果 68.75%的骨肉瘤患者CD13高表达,而仅有15.00%的良性骨瘤患者CD13蛋白高表达,经χ2检验,差异具有统计学意义(χ2=30.825,P0.001);CD13蛋白水平与骨肉瘤分期有关,Ⅲ期患者的CD13阳性率明显高于Ⅰ/Ⅱ期患者(χ2=4.981,P=0.026);CD13蛋白水平与骨肉瘤患者的年龄、性别、肿瘤直径、肿瘤部位等因素无明显相关(P0.05)。骨肉瘤组织中CD13的m RNA表达量明显高于癌旁组织,差异具有统计学意义(P0.001)。结论 CD13与骨肉瘤组织的发生发展具有一定的相关性。     

卵巢癌、绒癌等肿瘤患者外周血染色体畸变和脆性部位的观察

采用低叶酸、低胸腺嘧啶苷的培荐条件，对21例卵巢癌、绒癌等肿瘤和20例正常人淋巴细胞染色体脆性部位连行观察．结果表明，4种肿瘤患者的染色体脆性部位检出率高于对照组．其脆性部位有17个属结构性脆点，5个属遗传性脆点，有7个与癌断裂点和癌基因同在一区带上，有13个脆性部位与癌断裂点相一致．提示脆性部位与卵巢癌等有相关性．。     

人精子和淋巴细胞染色体脆性部位的表达

根据Sutherland 1979年提出的脆性部位的定义,至少有104种普通脆性部位(c-fra)、罕见脆性部位(r-fra)或有争议脆性部位(c-r-fra)被描述。并且认为染色体脆性部位是对受害者子代影响的一个危险因素。因为在一些病例中,带有染色体脆性部位个体的子代中发现有非整倍体和原发性结构重排的改变。但这些重排中的断裂点与其父母表达的脆性部位并不一致。所以对这些个体来说,分析精子染色体脆性部位是     

Chromosome instability in lymphocytes from two patients affected by three sequential primary cancers: the role of fragile sites

The chromosomal aberration rate and the expression of fragile sites induced by aphidicolin were evaluated in metaphase chromosomes obtained from peripheral blood lymphocytes of two untreated patients with multiple primary cancers. Spontaneous aberrations of chromosome number and structure and chromosome fragility were compared with controls with the use of the same methods. Chromosomal aberration rates and expression frequencies of fragile sites were significantly higher in the patients than in normal control subjects. In the patients, all but one structural chromosome aberration involved at least one fragile site. Our results suggest that fragile sites may be unstable regions of the human genome, which might play an important role in the genetic instability associated with cancer predisposition.     

Autosomal folate sensitive fragile sites in normal and mentally retarded individuals in Greece

The frequencies of autosomal folate sensitive fragile sites were compared in populations of mentally retarded fra(X) negative (N = 220) and normal children (N = 76) in Greece. In addition, the frequency of autosomal fragile sites was studied in 20 known fra(X) children in order to test if the fra(X) syndrome is associated with general chromosome instability. The frequencies of both common and rare autosomal fragile sites did not differ significantly between the mentally retarded and the normal children, although the rate of expression was considerably higher in the retarded group. Autosomal fragile sites were not increased in the fra(X) patients. Fra(3)(p14) was by far the most frequent one in all groups. The frequency of fra(6)(q26) was found to be considerably higher among the mentally retarded children, this difference being almost statistically significant. Further cytogenetic studies of normal and retarded individuals are required in order to elucidate this point further.     

Fragile sites: overview, occurrence in acute nonlymphocytic leukemia and effects of caffeine on expression

Interest has recently grown in the possible role of chromosomal fragile sites as factors predisposing to chromosome rearrangements characteristic of specific human cancers. Data from two series of experiments relating to this hypothesis are presented. First, the effects of caffeine and theophylline on expression of the fragile X and common fragile sites was studied in lymphocytes from three subjects. Caffeine and theophylline did not enhance fragile X expression under the conditions employed but did greatly enhance expression of the common fragile sites. Second, three patients with acute nonlymphocytic leukemia-M4 and inv(16)(p13q22) in leukemic cells were tested for the presence of fra(16)(q22) in normal cells. The fragile site was not seen in any of the patients in this study.     

Chromosome abnormalities and rare fragile sites detected in azoospermia patients

Summary We have examined constitutional chromosome abnormalities and fragile sites in 40 patients with azoospermia. Chromosome abnormalities were found in four cases. Three cases showed a deletion of the long arm of the Y chromosome 46,X,del(Yq) and the other case had a ring of G group chromosome 46,XY,r(G). In a rare fragile sites test, four fragile site carriers were detected and three rare autosomal fragile sites were identified; fra(8)(q24.1), fra(11)(p15.1), and fra(17)(p12). The expression of these fragile sites were induced specifically by AT-specific DNA ligands, such as distamycin A and Hoechst 33258. In addition, one patient was found to be the case of double ascertainment of fragile sites, fra(8)(q24.1) and fra(17)(p12). The overall frequency of distamycin A-inducible fragile sites in azoospermia patients appeared to be higher than those reported for Japanese healthy subjects and cancer patients. However, no significant relation among fragile sites, clinical and histological findings has been detected so far.     

Fragile sites at 4q23 and 7q11.23 unique to bone marrow cells

Fragile sites in chromosome bands 4q23 and 7q11.23 were discovered in bone marrow cells. Expression of these fragile sites was induced by treatment of the cells sequentially with 10(-7) M methotrexate and then 10(-5) M thymidine. No expression was observed in bone marrow cells without treatment. The fragile sites at 4q23 and 7q11.23 were seen individually, together, and in the homozygous state in a total of 20 bone marrow samples. The bone marrow karyotypes were normal in all cases. Expression of these common fragile sites at 4q23 and 7q11.23 could not be induced in blood lymphocytes from two subjects using methotrexate and thymidine, or by any other means including the addition of bromodeoxyuridine and fluoro-deoxyuridine or growth in folate-deficient medium. Because the fragile sites at 4q23 and 7q11.23 have never been observed in lymphocytes treated with methotrexate and thymidine for high-resolution chromosome analysis, it appears that these fragile sites are not expressed under these conditions in T lymphocytes. We propose that the differential expression of these fragile sites in bone marrow cells reflects genes active in bone marrow cells but not in blood lymphocytes.     

Common fragile sites in couples with recurrent spontaneous abortions

Recently, increased spontaneous chromosome instability was reported in couples with recurrent spontaneous abortions but without constitutional chromosome aberrations. Therefore, we investigated the frequency and distribution of aphidicolin-induced common fragile sites in couples with recurrent spontaneous abortions and no children and in age-related control couples. The breakage rate was significantly elevated in the abortion-prone couples; the women in the abortion couples had an especially higher breakage rate than the control women. Breakpoints cluster to those chromosome regions where common fragile sites have been localized. No preference of a particular common fragile site was demonstrated in the abortion couples. Our findings appear to support the hypothesis of increased chromosome instability in at least some couples with recurrent spontaneous abortions. As long as the nature of aphidicolin-induced common fragile sites is not completely understood, the significance of these findings remains unclear.     

Enhanced expression of chromosome fragile site 10q25 in chronic myelogenous leukemia

Spontaneous expression of a BrdU-sensitive fragile site at 10q25 was observed in normal lymphocytes and malignant blood and bone marrow cells in chronic myelogenous leukemia (CML). The cells were marked by a Philadelphia chromosome rearrangement due to insertion of 22q11----q13 at 11q13. The fragile site at 10q25 was expressed in larger proportions of malignant than normal cells. Although this fragile site is not at a cancer chromosome breakpoint, malignancy enhanced its expression, consistent with a cascade effect.     

Nature of distamycin A-inducible fragile sites

Five rare distamycin A-inducible fragile sites have been identified on human chromosomes: fra(8)(q24.1), fra(11)(p15.1), fra(16)(p12.1), fra(16)(q22), and fra(17)(p12). All of these fragile sites are located at the junction of Giemsa-positive (G) and negative (R) bands and their expression can be induced by a variety of AT specific DNA ligands. Analysis of family data indicate that the distamycin A-inducible fragile sites segregate as a simple codominant trait with complete penetrance, and probands receive these fragile site genes equally from mothers and fathers. Based on current knowledge of chromosome instability, the nature of distamycin A-inducible fragile sites is discussed. Distamycin A-inducible fragile sites appear to be unique chromosomal regions particularly susceptible to fragility under certain stress conditions. They may also be hot spots for recombination, gene amplification, and integration of foreign genomes.     

Two different structural abnormalities of chromosome 13 in offspring of chromo-somally normal parents with two fragile sites

Two siblings were found with different structural abnormalities involving their maternally inherited chromosome 13. The proband exhibited a ring 13 and a small fragment: 46, XX, r(13) (pllq34), +f, while her clinically normal brother carried a dicentric Robertsonian translocation: 45, XY, dic(13;15) (pl 1;pl 1). Both parents had normal karyotypes in peripheral blood and skin fibroblasts. The structural abnormalities of chromosome 13 may be due to an unstable gonadal 13; 15 translocation in the mother. In addition, two autosomal fragile sites were segregating in this family. The mother had a fragile (16) (q22) which was inherited by the proband. The father and paternal grandmother possessed a fragile (12)(q13) which was not inherited by either child. The expression of both fragile sites was dependent on culture conditions.