Klinefelter 综合征的临床与细胞遗传学分析

分析和探讨Klinefelter综合征的，临床以及细胞遗传学特征，通过遗传咨询和染色体核型综合分析进行疾病的诊断。确诊Klinefelter综合征88例，年龄13天-48岁，其中〈1岁3例，占3．4％；1～12岁11例，占12．5％；13～18岁6例，占6．8％；〉18岁68例，占77．3％。睾丸小是Klinefelter综合征最典型的表现。青春发动期以前难以发现。核型为47，XXY（包括变异）77例，占87．5％；嵌合型8例，占9．1％；48，XXYY2例，占2．3％；49，XXXXY1例，占1．1％，细胞遗传学染色体核型分析为确诊的主要手段。     

非霍奇金淋巴瘤的临床与骨髓细胞遗传学分析

目的研究非霍奇金淋巴瘤（non-Hodgkin lymphoma，NHL）的细胞遗传学、血液病理学、血液形态学、临床肿瘤指标与预后的相互关系。方法应用骨髓直接法和24h短期培养法制备染色体标本，用R显带技术，对20例NHL患者进行核型分析。所有患者均进行血清P53蛋白检测。结果20例NHL中出现骨髓浸润8例。20例NHL中，发现有异常核型9例，发生率45％（9／20）。异常类型包括：染色体数目异常3例，t（14，18）（q32；q21）1例，14q＋1例，t（8；14）（q24；q32）2例，t（8；14）（q24；q32）伴其他异常2例。伴异常核型的患者其血清P53蛋白含量显著高于正常核型者。结论t（8；14）（q24；q32）是NHL中涉及较多的染色体核型异常，伴此种核型异常的NHL患者预后不良，同时发现正常核型缺乏对预后也有不良影响。突变型P53值的增高和染色体核型异常有一定的相关性，也是预后不良的因素。     

Numerical chromosomal aberrations in prostate cancer: correlation with morphology and cell kinetics

Eleven routinely processed radical prostatectomy specimens were studied for the presence of numerical chromosomal aberrations by means of in situ hybridization with nucleic acid probes specific for chromosomes 7, 10, 17, X, and Y. Cytogenetic information was correlated with morphology, tumour stage and volume as well as with cell kinetics, the latter being assessed by immunohistochemistry with antibodies raised against the proliferative cell nuclear antigen (PCNA) and against a formalin-resistant epitope of the Ki-67 antigen, MIB 1. In 5 of 11 cases, numerical aberrations of at least one chromosome were found. The cases with normal chromosome numbers were those with the smallest volumes of Gleason grade 4 and/or 5 tumour (mean 0.5 cm³) and represented tumours restricted to the prostate. Tumours with aberrations in the number of detected chromosomes showed advanced stages and large volumes of high-grade tumour (mean 12.5 cm³). All 4 tumours with positive surgical margins were recruited from a group with marked local heterogeneity in chromosome numbers. Immunostaining with MIB 1 and PCNA was most intense in areas of high-grade tumour and was positively correlated with the emergence of chromosomal aberrations. The data suggest that the appearance of numerical chromosomal aberrations in prostate cancer coincides with aggressive tumour behaviour and could be used as an additional prognostic marker.This work is part of E.K.'s doctoral thesis     

Live imaging of rapid chromosome movements in meiotic prophase I in maize

The ability of chromosomes to move across the nuclear space is essential for the reorganization of the nucleus that takes place in early meiotic prophase. Chromosome dynamics of prophase I have been studied in budding and fission yeasts, but little is known about this process in higher eukaryotes, where genomes and chromosomes are much larger and meiosis takes a longer time to complete. This knowledge gap has been mainly caused by difficulties in culturing isolated live meiocytes of multicellular eukaryotes. To study the nuclear dynamics during meiotic prophase in maize, we established a system to observe live meiocytes inside intact anthers. We found that maize chromosomes exhibited extremely dynamic and complex motility in zygonema and pachynema. The movement patterns differed dramatically between the two stages. Chromosome movements included rotations of the entire chromatin and movements of individual chromosome segments, which were mostly telomere-led. Chromosome motility was coincident with dynamic deformations of the nuclear envelope. Both, chromosome and nuclear envelope motility depended on actin microfilaments as well as tubulin. The complexity of the nuclear movements implies that several different mechanisms affect chromosome motility in early meiotic prophase in maize. We propose that the vigorous nuclear motility provides a mechanism for homologous loci to find each other during zygonema.     

Usefulness of routine conventional cytogenetic analysis in tissues submitted for “lymphoma work-up”

Non-Hodgkin lymphomas (NHLs) are often characterized by specific cytogenetic abnormalities. We evaluate the utility of routine cytogenetic studies in 261 “lymphoma work-ups”. These include 4 non-hematolymphoid malignancies and 257 hematolymphoid processes submitted over 3 years, including even those initially appearing benign by morphology and immunophenotyping. About 64/257 yielded no results and 5/78 “lymphoid hyperplasia/lymphadenitis” were abnormal; 3 of these 5 appeared clonal [1, shortly followed by follicular lymphoma (FL)]. Increasing FL grades showed decreased t(14;18)/increased del 6q abnormalities. 1/4 Burkitt lymphomas (BL) (i.e., an atypical BL) showed t(8;14) and t(14;18) (i.e., a double-hit). 1/4 post-transplant lymphoproliferative disorders (PTLD) showed abnormalities, confirming clonality. One “extramedullary hematopoiesis” with a previous myelodysplastic syndrome and 1 erythroblastic sarcoma showed abnormalities, confirming myelodysplasias (MDS). A monocytic sarcoma revealed a t(9;11)(p22;q23). Routine cytogenetic studies aid in “lymphoma work-ups” by (1) detecting rare abnormalities in cases without apparent malignancy, indicating close follow-up, (2) detecting abnormalities in FL correlating with increasing grade, (3) detecting co-existent t(8;14) and t(14;18) in BL, indicating a worst prognosis, (4) establishing clonality in PTLD and (5) establishing diagnoses of MDS or chloroma in tissues. The findings by the conventional karyotyping studies in many of these cases added significant data to the diagnostic cases, beyond morphologic and immunophenotypic findings, and were not amenable to directed fluorescent-in-situ hybridization studies.     

A survey of 22 individuals with Prader-Willi Syndrome in New South Wales

Abstract Twenty-two individuals with Prader-Willi Syndrome in New South Wales were surveyed. The results show that males were diagnosed at a significantly earlier age than females and suggest a recent trend towards earlier diagnosis. The advantages of early diagnosis are discussed. In those in whom cytogenetic studies had been performed, 47% were found to have a deletion involving chromosome 15q11–13. Profound neonatal hypotonia had been present in all cases. Obesity became apparent between 1.5 and 10 years (mean = 3.8 years). Facial dysmorphism was reported in 83% and acromicria in 100%. Sixty-two per cent of subjects were regarded as less pigmented than first degree relatives. Cognitive assessments were performed on nine subjects. Two (22%) were functioning in the normal range of intelligence. Behaviour problems, both food-related and non-food-related, were present in the majority and placed considerable stress on the family caring for the individual with Prader-Willi Syndrome.     

Use of Fluorescent in Situ Hybridization to Detect Trisomy 13 in Archival Tissues for Cytogenetic Diagnosis

The present report describes the use of molecular probes to investigate the chromosomal constitution of interphase nuclei of formalin-fixed, paraffin-embedded tissue from three infants with multiple congenital malformations and a provisional diagnosis of trisomy 13 in two. Fluorescent in situ hybridization with the probe for the 13 and 21 centromeric regions revealed five nuclear signals in two of the cases, indicating the presence of an extra chromosome, and only four nuclear signals in the other case. Only the two positive cases had phenotypic features consistent with trisomy 13. Routine cytogenetic analysis was performed on one child and confirmed an additional chromosome 13. The child without an extra chromosome had features consistent with Ivemark syndrome. This study demonstrates the utility of fluorescent DNA probes for the retrospective diagnosis of aneuploidies in archival material.     

Benign salivary gland tumors: A cytogenetic study of 21 cases

Cytogenetic findings of 21 benign salivary gland tumors, including 14 pleomorphic adenomas, 5 Warthin's tumors, 1 myoepithelioma, and 1 cystadenoma, are reported. The present study confirms that pleomorphic adenomas characteristically have highly specific rearrangements involving only a few chromosome regions (3p21, 8q12 and 12q13–15) which suggests their specific role in the mixed tumors genesis. Warthin's tumors also show nonrandom numerical and structural alterations that were concurrent in one of the cases studied. To our knowledge no cytogenetic data are available in myoepitheliomas and cystadenomas. The former reveals a normal karyotype and the latter shows only clonal numerical alterations (gain of chromosomes 2 and 18). © 1995 Wiley-Liss, Inc.     

Classification of peripheral t-cell lymphomas: cytogenetic findings support the updated kiel classification

The cytogenetic findings in peripheral T-cell lymphomas enabled us to distinguish not only between low and high grade peripheral T-cell lymphomas (PTL) but also between different morphologically defined subtypes. High grade lymphomas exhibited a higher frequency of aberrant clones, polyp loid chromosome numbers, a higher complexity of aberrant clones and a lower proportion of normal metaphases than low grade PTL. Moreover, deletions in 6q, trisomies of 7q and monosomy I3 or changes of 13q 14 were significantly more frequent in high grade than in low grade PTL. Translocation t(2;5)(p23;q35) was only seen in large cell anaplastic lymphoma. T-CLL/T-PLL was associated with the simultaneous presence of inversion inv(14)(ql lq32. I) and trisomy 8q, mostly due to i(8q)(q10). Trisomy 3 was a characteristic chromosome aberration of lymphoepithelioid lymphoma, AILD-type T-cell lymphoma and T-zone lymphoma. In contrast to the other low grade PTL, AILD-type T-cell lymphoma and cutaneous T-cell lymphoma showed a high frequency of unrelated clones. In summary, the cytogenetic findings paralleled the histopathologic classification according to the updated Kiel classification and support the value of the distinction of the different morphologically defined entities.