结直肠癌患者外周血染色体脆性位点研究

目的研究结直肠癌的发生机理,期望发现与结直肠癌发生有关的染色体脆性位点,以指导结直肠癌高危人群的筛查和防治.方法对50例结直肠癌患者和50例健康正常人外周血淋巴细胞染色体脆性位点研究.结果50例结直肠癌患者中有32例的染色体结构有异常表达,结构畸变较常累及1号染色体,以1q11,1q21区的裂隙、断裂、重复最为常见,1q21与原癌基因SKI毗邻.结论1q21可能与结直肠癌的发生有关,并对结直肠癌高危人群的筛查和防治有一定的指导意义.     

食管癌组织染色体位点特异性的杂合性丢失和微卫星DNA序列不稳定

为了寻找在食管癌中发生缺失的染色体位点，根据以往细胞遗传学的工作基础，选取２４个分别位于１、２、３、５、７、９、１１、１７号染色体的食管癌染色体畸变＂热点＂及已知基因的位点，以微卫星序列－ＰＣＲ法检测这些位点处的杂合性丢失和微卫星序列不稳定。对３６对来自北京和山西阳泉的散发食管癌标本和相应正常组织的检测结果显示：在对应于９ｐ２２－２３、３ｐ１４．２、２ｐ２２、３ｐ２４－２６、１１ｑ１３．１、３ｐ２３、３ｐ２１．３、７ｑ３５、３ｑ２１－２２等染色体位点处存在较高频率（＞２０％）的杂合性丢失。同时，发现了染色体位点特异的微卫星ＤＮＡ不稳定。杂合性丢失和微卫星ＤＮＡ序列不稳定可能与食管癌的发生、发展过程有关。     

人胰腺癌组织3、5、7、9和18号染色体部分位点的杂合性丢失

目的了解人胰腺癌组织３、５、７、９和１８号染色体部分位点的杂合性丢失的状况。方法选择来自３、５、７、９和１８号染色体不同位置的９对多态性引物，对４５例胰腺癌存档石蜡标本经显微镜下剥离后，以ＰＣＲ－ＳＳＬＰ－银染法检测胰腺癌中这些位点的杂合性丢失。结果胰腺癌组织在１８ｑ２１．１、３ｐ１４．２、３ｐ２１．１和９ｑ２２－３１等处存在较高频率的杂合性丢失。结论胰腺癌的发生和发展可能涉及这些部位基因的改变     

B细胞恶性肿瘤中染色体易位分子机制的研究

在Ｂ细胞恶性肿瘤中已经发现许多染色体异常，其中多数为染色体易位，较常见为ｔ（８；１４）（ｑ２４；ｑ３２）、ｔ（５；１４）（ｑ３１；ｑ３２）、ｔ（１１；１４）（ｑ１３：ｑ３２）、ｔ（１４；１８）（ｑ３２；ｑ２１）、ｔ（１４；１９）（ｑ３２；ｑ１３）、ｔ（１；１９）（ｑ２３；ｐ１３）、ｔ（１７；１９）（ｑ２２；ｐ１３）、ｔ（４；１１；）（ｑ２１；ｑ２３）。在一般情况下，这些染色体易位的一方累及免疫球蛋     

食管癌组织染色体位点特异性的杂合性丢失和微卫星DNA序…

为了寻找在食管癌中发生缺失的染色体位点，根据以往细胞遗传学的工作基础，选取２４个分别位于１、２、３、５、７、９、１１、１７号染色体的食管癌染色体畸变“热点”及已知基因的位点，以微卫星序列－ＰＣＲ法检测这些位点处的杂合性丢失和微卫星序列不稳定。对３６对来自北京和山西阳泉的散发食管癌标本和相应正常组织的检测结果显示：在对应于９ｐ２２－２３、３ｐ１４．２、２ｐ２２、３ｐ２４－２６、１１ｑ１３．１、３ｐ２     

福州地区113例智力低下者的染色体检查及分析

本文对１１３例智力低下者的染色体检查结果进行分析。５０例染色体异常,异常率为４４２５％,２１－三体仍居首位,占３３７１％。１３ｑ三体２例,比较核型４６,ＸＸ／４６,ＸＸ,－１３,＋ｔ（１３ｑ;１３ｑ）及４６,ＸＸ,－９,＋ｔ（９ｑ;１３ｑ）,前者为单纯１３ｑ三体,后者除１３ｑ三体外,伴有９ｐ单体,提出造成智力低下的主要原因为１３ｑ三体,致病位点可能位于１３ｑ上。异态性７例,其中４６,ＸＸ（ＸＹ）３例,其它４例,认为染色体的异态性可能亦与中枢神经系统的发育完善有关。     

B细胞恶性肿瘤中染色体易位分子机制的研究

在Ｂ细胞恶性肿瘤中已经发现许多染色体异常，其中多数为染色体易位，较常见为ｔ（８；１４）（ｑ２４；ｑ３２）、ｔ（５；１４）（ｑ３ｌ；ｑ３２）、ｔ（ｌｌ；１４）（ｑｌ３：ｑ３２）、ｔ（１４；１８）（ｑ３２；ｑ２１）、ｔ（１４；１９）（ｑ３２；ｑ１３）、ｔ（１；１９）（ｑ２３；ｐｌ３）、ｔ（１７；１９）（ｑ２２；ｌ７１３）、ｔ（４；１１）（ｑ２１；ｑ２３）。在一般情况下，这些染色体易位的一方累及免疫球蛋白（Ｉｇ）基因或Ｅ２Ａ基因，而另外一方累及一个潜在的原癌基因。已知Ｉｇ和Ｅ２Ａ基因都是与Ｂ淋巴细胞密切关联的基因，由于染色体易位，导致这些原癌的基因的活化，可能与Ｂ细胞恶性肿瘤的发生和发展有着密切的关系。     

染色体脆性位点的研究进展

１９６５年，Ｄｅｋａｂａｎ首次报道了人类染色体上的第一个脆性位点［１］，但脆性位点一词直到１９７０年才提出，如今已有１１４种脆性位点被发现。在这些研究中，有两个重大发现起了促进作用，第一是在人类的Ｘ染色体上发现了一个脆性位点ｑ２７．３，它和Ｘ连锁的智力低下有关；第二是摸清了制备染色体标本过程中培养细胞的特殊条件，经过各种处理能得到不同的脆性位点。８０年代，有大量的关于脆性位点的文章出现，绝大多数…     

脑膜瘤细胞和分子遗传学研究进展

脑膜瘤是中枢神经系统常见肿瘤，细胞遗传学研究已证实２２号染色体丢失为脑膜瘤克隆演化过程中最恒定的染色体异常，其它染色体丢失或重排的核型演化，可能与临床浸润过程有关。分子遗传学研究主要集中于２２号染色体长臂，推测２２ｑ１１－ｑ１２和ｑ１２．３－ｑｔｅｒ区域存在肿瘤抑制基因，其丢失或突变可能与脑膜瘤病因学相关。同时，癌基因ｃ－ｓｉｓ、ｃ－ｍｙｃ的过度表达可能参与诱发脑膜瘤。     

脑膜癌细胞和分子遗传学研究进展

脑膜瘤是中枢神经系统常见肿瘤，细胞遗传学研究已证实２２号染色体丢失为脑膜瘤克隆演化过程中最恒定的染色体异常，其它染色体丢失或重排的核型演化，可能与临床浸润过程有关。分子遗传学研究主要集中于２２号染色体长臂，推测２２ｑ１１－ｑ１２和ｑ１２．３－ｑｔｅｒ区域存在肿瘤抑制基因，其丢失或突变可能与脑膜瘤病因学相关。同时，癌基因ｃ－ｓｉｓ、ｃ－ｍｙｃ的过度表达可能参与诱发脑膜瘤。     

Molecular cytogenetic mapping of recurrent chromosomal breakpoints in tenosynovial giant cell tumors

Tenosynovial giant cell tumor (TGCT) is the most common benign tumor of synovium and tendon sheath. Cytogenetic data indicate that 1p11-13 is the region most frequently involved in structural rearrangements. With the aim of eventually identifying the genes associated with TGCT development, we have investigated 1p11-13 breakpoints using fluorescence in situ hybridization (FISH) analysis, with a panel of yeast artificial chromosome (YAC) probes covering 1p11-21. Twenty-six tumors were analyzed by G-banding, and 24 of these showed a breakpoint in 1p11-13. The cytogenetic findings add to previous observations that, among a variety of translocations involving 1p11-13, chromosome 2 is the most common translocation partner, with a breakpoint in 2q35-37. This aberration was found in eight cases. Other recurrent translocation partners, found in two or three cases, were 5q22-31, 11q11-12, and 8q21-22. Material from 21 tumors was available for FISH analysis, which revealed that the breakpoints clustered to one region spanned by two YAC probes, 914F6 and 885F12 located in 1p13.2, in 18 cases. Bacterial artificial chromosome probes were used to map the recurrent breakpoint on chromosome 2. In four of seven cases there was a breakpoint within the sequence covered by probe 260J21, where the RDC1 gene is located, a gene reported to fuse with HMGIC in lipomas with a 2;12 translocation.     

Specific chromosome anomalies and predisposition to human breast, renal cell, and colorectal carcinoma

Specific chromosome abnormalities in three human solid tumors of adulthood--renal cell carcinoma, breast tumor, and colon carcinoma--are described. Two of the neoplasms are associated with a reciprocal translocation involving chromosome #3 (breakpoint at band p13-14 with 6, 8, 11, and 16) in renal cell carcinomas and chromosome #1 (breakpoint at band q21 with chromosomes #3, #5, #10, #11, and #12) in breast carcinomas. Most of these chromosomal rearrangements have been seen as tumor-specific acquired changes in tumor cells, as well as some constitutionally present in normal tissues of patients. In a limited number of colorectal carcinoma samples a deletion in the short arm of a chromosome #12 is implicated as a specific abnormality. The expression of fragile sites in these specific chromosomal regions in the normal peripheral blood cultures might identify an individual predisposed to develop a particular type of neoplasm.     

A constitutional bws-related t(11;16) chromosome translocation occurring in the same region of chromosome 16 implicated in wilms' tumors

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder with a varying spectrum of clinical manifestations including macroglossia, omphalocele, hemihypertrophy, and a predisposition to a subset of embryonal tumors, most frequently Wilms' tumor (WT). A variety of cytogenetic, genetic linkage, and molecular mapping data implicate a gene or genes on chromosome band 11p15.5 in BWS and its related tumors. However, some families with BWS do not show linkage to 11p15, and other alterations have been found in Wilms' tumors as well. One such alteration is loss of heterozygosity (LOH) for chromosome arm 16q. Here we have analyzed a balanced t(11;16)(p15;q13) chromosomal translocation associated with the BWS phenotype and mapped the breakpoint positions for both chromosomes 11 and 16 by using somatic cell hybrids and polymorphic markers. The chromosome 11 breakpoint was found to lie distal to the D11S12 locus, but proximal to TH on 11p15.5, a region shown previously to contain other BWS-related chromosomal events. The chromosome 16 breakpoint was distal to D16S290 in 16q13, but proximal to loci D16S265, D16S267, and D16S164 in band 16q21. This area encompasses the region of LOH occurring through mitotic recombination in sporadic WT. This raises interesting possibilities for the genetic and epigenetic involvement of both chromosomal regions (11p15 and 16q13) in the pathogenesis of BWS and Wilms' tumor.     

A new case of 2q duplication supports either a locus for orofacial clefting between markers D2S1897 and D2S2023 or a locus for cleft palate only on chromosome 2q13-q21

We report on a pure duplication of the proximal chromosome 2q in a 6.5-year-old boy with V-shaped midline cleft palate and bifid uvula, posteriorly located tongue, and micrognathia (Pierre Robin sequence), celiac disease, failure to thrive, and developmental delay. Cytogenetic and FISH analysis indicated a duplication of chromosome 2q13-q22. In general, pure proximal duplication or triplication of 2q is rare. The clinical features and chromosomal breakpoints of the 10 previously reported patients varied, and no common phenotype or proximal duplication/triplication 2q syndrome could be defined to date. However, based on four previous patients with different orofacial clefts and our case, a locus for orofacial clefting may be located at proximal 2q. The duplication/triplication comprised chromosome 2q13 in all five affected individuals including our patient. Our patient and three previous cases (two with cleft palate only (CPO) and one with cleft lip/palate (CL/P)) showed a cytogenetic breakpoint at 2q13, which could support the presence of a critical dominant gene disrupted by a common breakpoint, however, the fifth case with CPO showed different breakpoints, advocating against the disruption of a critical dominant gene and supporting that the overexpression of a gene(s) on chromosome 2q13-q21 may cause cleft palate only (CPO) and Pierre Robin sequence. Hence, our findings support either the presence of one locus for orofacial clefting (CL/P, CPO, and Pierre Robin sequence) between markers D2S1897 (chromosome 2q12.2) and D2S2023 (chromosome 2q14.2), or alternatively the presence of a locus for CPO and Pierre Robin sequence on chromosome 2q13-q21.     

Variant Philadelphia translocations in CML: correlation with fragile sites

Of 175 CML patients studied, 14 variants were found, seven of which are presently described. The breakpoints involved in the translocation, other than 9q34 and 22q11, are 3p21, 5q13, 6p21, 7q22, 10q22, and 11p13. Fragile sites were investigated in some of these patients. In two cases a coincidence between fragile site location and breakpoint of the third chromosome involved in Philadelphia formation was found. This observation suggests that the fragile sites can lead to Ph variants in patients developing CML.     

Molecular evidence for putative tumour suppressor genes on chromosome 13q specific to BRCA1 related ovarian and fallopian tube cancer.

BACKGROUND/AIMS: Loss of heterozygosity (LOH) on chromosome 13q has been reported to occur frequently in human ovarian cancer, and indications have been found that chromosome 13 may also play a specific role in the inherited form of ovarian cancer. The aim of this study was to define regions on chromosome 13 that may harbour additional tumour suppressor genes involved in the tumorigenesis of BRCA1 related ovarian and fallopian tube cancer. MATERIALS/METHODS: DNA extracted from paraffin wax blocks of 36 BRCA1 associated ovarian and fallopian tube carcinomas was analysed by LOH polymerase chain reaction using seven highly polymorphic microsatellite markers spanning chromosome 13q. RESULTS: High LOH frequencies were found on loci 13q11, 13q14, 13q21, 13q22-31, 13q32, and 13q32-4, suggesting the presence of putative tumour suppressor genes on the long arm of chromosome 13 that may play a role in the pathogenesis of BRCA1 related ovarian and fallopian tube cancer. LOH patterns appeared to be independent of the type of BRCA1 mutation, stage, and grade. Although in some cases there were indications for loss of larger parts of chromosome 13, in most cases losses were fairly randomly distributed over chromosome 13 with retained parts in between lost parts. Microsatellite instability was found in six cases. CONCLUSION: Several loci on chromosome 13q show high frequencies of LOH in BRCA1 related ovarian and fallopian tube cancer, and may therefore harbour putative tumour suppressor genes involved in the carcinogenesis of this particular type of hereditary cancer.     

Molecular cytogenetics localizes two new breakpoints on 11q23.3 and 21q11.2 in myelodysplastic syndrome with t(11;21) translocation.

Translocation t(11;21)(q24;q11.2) is a rare but recurrent chromosomal abnormality associated with myelodysplastic syndrome (MDS) that until now has not been characterized at the molecular level. We report here results of a molecular cytogenetic analysis of this translocation in a patient with refractory anemia. Using FISH with a panel of 11q and 21q cosmid/YAC probes, we localized the chromosome 11 breakpoint at q23.3 in a region flanked by CP-921G9 and CP-939H3 YACs, distal to the HRX/MLL locus frequently involved in acute leukemias. The chromosome 21 breakpoint was mapped in a 800-kb fragment inserted into the CP-145E3 YAC at 21q11.2, proximal to the AML1 gene. It is noteworthy that in all four cases with a t(11;21) reported until now, a second der(11)t(11;21) and loss of normal chromosome 11 could be observed either at diagnosis or during the course of the disease. Since in our case heteromorphism was detected by FISH on the centromeric region of the two der(11), the second der(11) chromosome could be the result of a mitotic recombination that had occurred on the long arm of chromosome 11, rather than of duplication of the original der(11). Constancy of secondary karyotypic changes resulting in an extra copy of the putative chimeric gene at der(11), loss of 11 qter sequences, and partial trisomy 21 suggest that neoplastic progression of MDS cases with a t(11;21) may be driven by the same mechanism(s).     

Familial 14-Mb deletion at 21q11.2–q21.3 and variable phenotypic expression

We report a familial case with a proximal interstitial deletion of chromosome 21q [del(21q)]. Although the mother in the family was phenotypically normal, her first child was affected with both sensorineural hearing loss and moderate mental retardation, and the second affected child had mild mental retardation but not sensorineural hearing loss. We determined breakpoints of the del(21q) in the mother and her two affected children by fluorescence in situ hybridization analysis using 45 DNA clones and the molecular analysis using 21 DNA markers. The proximal breakpoint of the del(21q) was located at a region between 0.33 Mb and 0.46 Mb distal to the centromere, and the distal breakpoint was at a region between 14.6 Mb and 14.9 Mb. The finding indicates that the three individuals had an approximate 14-Mb deletion within 21q11.2–q21.3. Molecular analysis showed that both affected children shared the same maternal haplotype of their del(21q), but a crossover was detected in the paternally inherited normal chromosome 21. These data suggest that unmasking of deleterious genes on the paternally derived chromosome 21 of the two children as a result of the deletion may affect the extent of their mental retardation and/or sensorineural hearing loss. Usher syndrome 1E may be a candidate disease locus related to the sensorineural hearing loss of the first child. Received: March 1, 2002 / Accepted: June 14, 2002     

Chromosomes in retinoblastoma patients

In a series of eight patients with retinoblastoma, one was found to have a reciprocal translocation of chromosomes 1 and 13. The breakpoint on chromosome 13 is at band q12, which suggests that the retinoblastoma locus is less distal than previously thought.