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[Cytogenetic analysis in the definition and classification of non-Hodgkin's lymphomas].

Cytogenetic analysis of Non-Hodgkin's Lymphomas (NHL) taken together with immunophenotypic and genotypic studies, may contribute to better define their morphologic classification. In this review the main cytogenetic data have been summarized, looking at a histopathologic NHL categorization that is related to a modern multiparametric approach. The correlation of non random chromosome abnormalities with NHL categories will augment information about their pathogenesis and tumor progression.

Aneuploidy↗

Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors.

We report the cytogenetic analysis of 124 adult male germ cell tumors ascertained consecutively at the Memorial Sloan-Kettering Cancer Center between 1988 and 1990. Biopsies from testicular and extragonadal primary and metastatic lesions studied included all histological subtypes of germ cell tumors and cases of malignant transformation. Nonrandom numerical and structural chromosomal abnormalities including i(12p), the previously described characteristic marker of these tumors, were determined, and their frequency was compared between histological subtypes, between gonadal and extragonadal lesions, and between primary and transformed lesions. The frequency and copy number of i(12p) were found to be higher in nonseminomas compared with seminomas. Nonrandom sites of chromosome rearrangements associated with specific histologies comprised 1p32-36 and 7q11.2 in teratomas and 1p22 in yolk sac tumors. Some tumors that underwent malignant differentiation exhibited chromosome changes previously described to be nonrandomly associated with de novo tumors with the same histological characteristics. Cytological evidence of gene amplification in the form of homogeneously staining regions and/or double minutes was detected in 24% of extragonadal lesions, mainly metastatic tumors, suggesting amplification of a gene(s) associated with metastatic progression of these tumors. While a number of previous small cytogenetic series or individual case reports of germ cell tumors identified several of the features of these tumors reported here, this series comprises analysis of the largest group of tumors ascertained consecutively at a single institution, defines the incidence of nonrandom abnormalities in tumor subsets, and addresses their biological significance.

Cell Transformation, Neoplastic↗

Interphase cytogenetic analysis of 1q12 satellite III DNA in melanocytic lesions: increased aneuploidy with malignant histology.

To examine the relationship of chromosome 1 copy number to melanocytic tumorigenesis, interphase cytogenetic analysis of 1q12 satellite III DNA was performed on the spectrum of melanocytic lesions comprising Clark's tumor progression model. Results showed increased copy number in a "step off" pattern between melanoma in-situ and the intraepidermal component of invasive melanoma rather than a progression between each lesional group. These findings support Clark's concept of independent clonal expansion of a cell population giving rise to the vertical growth phase and further demonstrates increased chromosome 1 copy number as a late event in melanoma tumor progression.

Analysis of Variance↗

[Cytogenetic analysis of 19 renal cell tumors].

To further evaluate the role of cytogenetic analysis we studied 19 cases of renal neoplasms. Specific chromosomal aberrations have been demonstrated associated with different histologic types. Particularly, clear cell renal cancers were associated with deletions of the short arm of chromosome 3 and papillary renal cell cancers demonstrated multiple trisomies, and chromophobe cancers and oncocytomas were characterized by loss of whole chromosomes. The utility of cytogenetics as a tool to define the pathological spectrum of renal cell neoplasms is stressed.

Adult↗

Cytogenetic analysis of BC2, a new human hepatoma cell line, by fluorescent in situ hybridization.

Cytogenetic analysis of a new human hepatoma cell line BC2 was performed with conventional cytogenetic techniques and fluorescent in situ hybridization. Numerical and structural abnormalities were observed by conventional cytogenetics for chromosomes 1, 2, 4, 7, 8, 9, 10, 11, 15, 17 and 20. Chromosome painting allowed to specify the translocation of chromosome 1, and to characterize 3 markers from chromosome 8 and one marker from 9, which were unrecognizable by conventional techniques. Comparison of chromosome 1 abnormalities with those reported in the literature for other human hepatoma cell lines showed that structural abnormalities of chromosome 1 were present in different regions of this chromosome. A review of the literature was done, and the results discussed, suggesting that alterations of chromosome 1 may be important in hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

Cytogenetic analysis of invasive breast cancer: a study of 27 Asian patients.

Tumor cytogenetic analysis from 27 patients with breast cancer diagnosed at the Singapore General Hospital revealed complex karyotypic aberrations in 12 cases. The study group comprised 25 women and 2 men, ranging in age from 33 to 78 years (median 52 years). Ethnic distribution consisted of 22 Chinese, 3 Malaysian, and 2 Indian patients. Pathologic assessment disclosed 24 invasive ductal, 2 invasive mucinous, and 1 mixed invasive mucinous and ductal carcinomas. Histologic grading showed 3 grade 1, 10 grade 2, and 12 grade 3 tumors; 2 cancers were not graded, because they had been subjected to prior chemotherapy. Tumor sizes ranged from 1.5 to 10 cm (median 3 cm). Eleven cases were axillary node negative, whereas the remaining 16 node-positive cancers affected as many as 3 nodes in 8 cases and 4 or more nodes in another 8. Twenty cases demonstrated estrogen-receptor positivity, and 8 cases progesterone-receptor positivity. The spectrum of cytogenetic abnormalities involved chromosomes 1, 3, 6, 7, 8, 11, 16, and 17 and ranged from gains and deletions of both long and short arms, trisomy, monosomy, and other rearrangements. There was a trend toward the presence of karyotypic abnormalities in tumors of higher grade.

Adenocarcinoma↗

Cytogenetic analysis of experimental hybrids in species of Triatominae (Hemiptera-Reduviidae).

A cytogenetic analysis was performed in experimental hybrids between species of Chagas disease transmitting bugs with remarkable differences in the amount and distribution of heterochromatin. Using C-banding technique, we identified the parental species chromosomes and analysed the meiotic behaviour in the male hybrids between Triatoma platensis and T. infestans, T. platensis and T. delpontei, and T. infestans and T. rubrovaria. The two former hybrids have an entirely normal meiotic behaviour despite the extensive differences in C-banded karyotypes observed in the parental species, indicating that heterochromatin differences between homeologous chromosomes are not a barrier that influences meiotic synapsis and recombination. On the contrary, the experimental hybrids between T. infestans and T. rubrovaria show failures in pairing of homeologous chromosomes that lead to the production of abnormal spermatids and hybrid sterility. Our data suggest that karyotypic repatterning within triatomines has involved at least two different pathways. Among closely related species, chromosomal changes have largely involved addition or deletion of heterochromatic regions. In more distant species, chromosomal rearrangements (i.e. inversions and translocations) have also arisen. Hybridisation data also allow to hypothesize about the origin and divergence of this taxonomic group, as well as the mechanisms that maintain species isolation.

Animals↗

Molecular and cytogenetic analysis of familial Xp deletions.

Five families in which an Xp deletion is segregating and two families in which an X chromosome rearrangement including a deletion of the short arm is segregating were ascertained for study. Normal fertility was seen in all families. Members from 5 of the 7 families manifested short stature (height <5th centile), while normal height was present in two families. Studies of both the FMR-1 and the androgen receptor loci using PCR based X-inactivation analysis demonstrated that in all families analyzed, there is preferential inactivation of one X chromosome. Molecular cytogenetic analysis showed that members of 3 of the 7 families share a common breakpoint in an approximate 2-3 Mb region at Xp22.12, suggesting a possible hotspot for chromatin breakage. Previous genotype-phenotype correlations and deletion mapping have indicated that a gene for stature resides within the pseudoautosomal region in Xp22.33. Our findings indicate that the loss of this region is not always associated with short stature, suggesting that other factors may be involved.

Body Height↗

Cytogenetic analysis of short-term cultured squamous cell carcinomas of the lung.

Cytogenetic analysis of 122 primary squamous cell carcinomas of the lung revealed clonal abnormalities in 56 tumors. Karyotypes with simple numerical changes were found in 32 tumors: 45,X,-Y in 28, 47,XY,+7/45,X-Y, in two, 47,XY,+Y/45,X,-Y and 47,XY,+20/45,X,-Y in one tumor each. A super-numerary ring chromosome was the sole anomaly in two tumors. Complex structural changes were found in 22 tumors. The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (15 tumors), 3, 7, and 11 (10 tumors each), 5 and 6 (nine tumors each), and 2, 8, and 12 (eight tumors each). The bands and regions most often affected were 1p11-13 and 5cen (six tumors each), 11p11, 14p11-13, 15cen, and 17p11-12 (five tumors each), and 12p13 and 13cen (four tumors each). The only recurrent changes were the whole-arm rearrangements i(5)(p10) (five tumors) and i(6)(p10), der(9;15)(q10;q10), and der(13;15)(q10;q10) (two tumors each). The most prominent genomic imbalances were, apart from losses of the Y chromosome, losses from 1p, 3p, 5q, 6q, 8p, 13p, and 14p and gains from 1q and 5p.

Aged↗

Cytogenetic analysis of bovine parthenotes after spontaneous activation in vitro.

We conducted a cytogenetic study of bovine parthenotes derived from oocytes matured and cultured in vitro. In vitro maturation was carried out by culturing follicular oocytes for 24 h in TCM199 supplemented with estrous cow serum (ECS) and hormones at 39 degrees C in 5% CO2. Matured oocytes were incubated for 20 h in sperm TALP without the addition of spermatozoa, after which they were cultured in maturation droplets for 48 to 72 h. Spontaneous activation occurred in 9.5% of the matured oocytes. Cytogenetic analysis of 24 parthenotes revealed that 62.5% exhibited a normal, diploid chromosome complement. The remaining 37.5% had various ploidy anomalies: haploidy (25%), triploidy (4.2%) and tetraploidy (8.3%). Parthenotes exhibited different developmental stages. The number of blastomeres ranged from 2 to 8 within a parthenote. Only 1 parthenote was comprised 9 to 16 cells. The results showed that spontaneous parthenogenetic activation which occurs in an IVM/IVF system may interfere with embryo production efficiency.

Animals↗

High-resolution cytogenetic analysis of X-ray induced mutations of the HPRT gene of primary human fibroblasts.

We report cytogenetic analysis of X-ray induced mutants of the HPRT gene isolated from a primary human fibroblast line. The mutants were shown previously by molecular analysis to have total or partial HPRT gene deletions. Detailed analysis of the chromosomal region containing HPRT (the cytogenetic band Xq26) identified Xq26 aberrations in five of five total HPRT gene deletions but failed to detect any changes in two of two partial gene deletions. Four microdeletions were verified and quantified by a method termed the band ratio, which compares the distance between bands encompassing Xq26 and an adjacent X-chromosome region in elongated chromosomes. These measurements were supported by the presence or absence of the sub-band Xq26.2. One total HPRT gene deletion was also associated with an X;11 translocation involving band Xq26. The data strengthen earlier findings on the tolerance of the Xq26 region to large genetic changes (> 1 Mb), but also indicate that some mutations are more complex than simple deletion of DNA sequence.

Cells, Cultured↗

Cytogenetic analysis of two C-1300 murine neuroblastoma cell lines expressing discordant malignant behavior.

Cytogenetic analysis of two murine neuroblastoma cell lines that show different malignant expression revealed consistent differences in the chromosomal composition between the two lines. The MNB-T1 (high-malignancy) cell line showed increased modal chromosome number, presence of homogeneously staining regions (HSRs), double minutes (dmin) and evidence of secondary chromosomal events when compared with the MNB-T2 (low-malignancy) cell line, which did not express these cytogenetic characteristics. Several of the cytogenetic events that have occurred in these murine cell lines, such as HSRs, dmin, and chromosomal deletions, have also been reported in human neuroblastoma cell lines. When comparisons are made for the involvement of chromosomal regions known to be involved in human neuroblastoma, similar tumor specific regions seem to be involved in the homologous mouse chromosomes.

Animals↗

A detailed cytogenetic analysis of large numbers of fresh and frozen-thawed human sperm after ICSI into mouse oocytes.

BACKGROUND: Since information about chromosome aberrations in micro-manipulated sperm is still inadequate, cytogenetic analysis was performed on large numbers of fresh and frozen-thawed (FT) human sperm after injection into mouse oocytes. The effects of the ICSI procedure on oocytes are also discussed based on analysis of the mouse chromosome complements. METHODS: After the injection of fresh and FT human sperm into mouse oocytes, chromosomes of the hybrid oocytes were analysed at first cleavage metaphase. RESULTS: Incidences of the hybrid oocytes at the first cleavage metaphase were significantly different between fresh (71.5%) and FT sperm groups (80.1%) (P < 0.05). The chromosome analysis of 477 fresh and 141 FT sperm showed no difference in the incidences of aneuploidy (1.6/0.7%), structural aberrations (8.8/7.8%) or diploidy (0.0/0.0%) between these categories. The cytogenetic result did not differ from our previous result using IVF between human sperm and hamster oocytes. In an additional cytogenetic study on 615 mouse chromosome complements, the incidence of diploidy (5.4%) was significantly higher than those (0.3-2.8%) in the previous mouse cytogenetic studies, and the hybrid oocytes with no mouse chromosomes (2.0%) existed. CONCLUSIONS: This result suggests that the ICSI procedure induces no sperm chromosome aberrations but increases numerical aberrations in oocyte chromosome complements.

Aneuploidy↗

Cytogenetic analysis of sperm from a male heterozygous for a 13;14 Robertsonian translocation.

Cytogenetic analysis of 121 sperm from a man heterozygous for a t(13;14) Robertsonian translocation was performed using the technique of in vitro penetration of hamster eggs. The frequency of sperm that were chromosomally unbalanced with respect to the translocation was 27%. The frequency of chromosomally normal (36%) and balanced (38%) complements was approximately equal, as theoretically expected. There was no evidence for an interchromosomal effect since the frequency of numerical chromosomal abnormalities (2.5%) and structural chromosomal abnormalities (10.7%)--both unrelated to the translocation--were within the normal range of control donors. The ratio of X- and Y-chromosome bearing sperm was equal, and there was no evidence for preferential segregation of the X chromosome with the translocation.

Adult↗

Cytogenetic analysis of a child with malignant histiocytosis.

This report presents the results of cytogenetic analysis of a child with malignant histiocytosis. The analysis was carried out on slides obtained following short-term cultures of peripheral blood cells. The malignant cells had a deletion of the long arm of chromosome #7, 46,XX,del(7)(q22).

Chromosome Banding↗

Cytogenetic analysis of children under long-term antibacterial therapy with nitroheterocyclic compound furagin.

Cytogenetic analysis of chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) was performed in 109 blood samples from 95 pediatric patients with urinary tract infections (UTIs). Children were exposed to diagnostic levels of X-rays during voiding cystourethrography and subsequently treated for one to 12 months with low doses of furagin - N-(5-nitro-2-furyl)-allylidene-1-aminohydantoin. Furagin is 2-substituted 5-nitrofuran, chemically and structurally similar to well-known antibacterial compound nitrofurantoin. Increased frequencies of CAs were found in children undergoing voiding cystourethrography as compared with the unexposed, acentric fragments being the most frequent alteration (2.03 versus 0.88 per 100 cells, P=0.006). However, a significant decrease in the frequency of acentric fragments was determined with the time elapsed since X-ray examination was performed. A time-independent increase in SCE frequency was found in lymphocytes of children treated with furagin. Total CA frequency did not differ significantly between groups of children with various duration of furagin treatment. However, frequency of chromatid exchanges (triradials and quadriradials) increased significantly with duration of treatment.

Anti-Infective Agents, Urinary↗

Cytogenetic analysis of erythroleukaemia in two children - evidence of nonmalignant nature of erythron.

Serial cytogenetic and cytological studies in 2 cases of erythroleukaemia in children indicated that erythropoiesis is not involved in the malignant process itself, but represents a response caused by unknown stimuli. A good correlation was observed between the percentage of aneuploid cells and blasts in mitosis, thus during the erythroid phase aneuploidy was minimal or absent, while during the myeloblastic phase a high percentage of members of the aneuploid clone was present. An inverse correlation between peripheral normoblast count and haemoglobin level indicated that erythropoiesis was under physiological control. Taken together these observations constitute evidence that, in the cases of erythroleukaemia studied, erythroid cells do not have inherent malignant properties. Cytogenetic analysis offers a tool for differentiating this type of erythroleukaemia from other forms of DiGuglielmo's syndrome.

Aneuploidy↗