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At least 595 records · Page 33Linked to original sources
PubMed2006

Relationship between point gene mutation, chromosomal abnormality, and tumour suppressor gene methylation status in colorectal adenomas.

Epigenetic mechanisms in carcinogenesis may have a significant role in the development of colorectal cancer. To investigate this phenomenon in early-stage disease, promoter methylation status in the tumour suppressor genes APC, MGMT, hMLH1, P14/P14ARF, and CDKN2A/P16 was investigated in 78 colorectal adenomas. These had previously been characterized for mutations of APC, KRAS, and TP53 genes and for chromosomal abnormality by comparative genomic hybridization (CGH). APC hypermethylation was seen in 52 tumours (66.7%). APC showed either methylation or mutation in 66 lesions (84.6%), but these events were not statistically associated. MGMT methylation was detected in 39 cases (50%). Adenomas with this abnormality showed a significantly lower number of chromosomal changes by CGH (p < 0.02), confirming that DNA repair defect of this type is associated with a lower level of chromosomal instability. An hMLH1 methylation defect was seen in only one adenoma (1.3%), from a patient who had a synchronous cancer showing the same defect. Methylation of P14 (P14ARF) was seen in 31 adenomas (39.7%) and CDKN2A (P16) abnormality in 25 (32.1%). DNA methylation at two or more loci was seen in 46 tumours (59%), while 11 lesions (14.1%) showed no evidence of hypermethylation at any of the loci studied. Methylation at any or all of MGMT, P14 or P16 was significantly associated with APC methylation (p = 0.01). Those neoplasms with more than two methylated genes showed significantly fewer chromosomal abnormalities than adenomas with one or no methylated loci (p < 0.001). There was no association between specific individual chromosomal abnormalities, APC, KRAS or TP53 mutations and any pattern of methylation abnormality. We conclude that methylation abnormality is very common in pre-invasive colorectal neoplasia, and that high level methylation is associated with low level chromosomal instability.

Adaptor Proteins, Signal Transducing↗
PubMed2001

The detection and significance of chromosomal abnormalities in childhood acute lymphoblastic leukaemia.

In childhood acute lymphoblastic leukaemia (ALL), cytogenetics plays an essential role in diagnosis and prediction of outcome. Conventional cytogenetic analysis, complemented by fluorescence in situ hybridization (FISH), is highly effective in the accurate detection of chromosomal abnormalities. For the precise identification of specific genetic changes, molecular techniques may be applied. Chromosomal changes in ALL may be of structural or numerical type. A large number of established structural chromosomal rearrangements have now been described for which the genetic alterations and effect on prognosis are well known. These include t(9;22)(q34;q11) and BCR/ABL, rearrangements of 11q23 involving MLL, t(12;21)(p13;q22) with the ETV6/AML1 fusion, t(1;19)(q23;p13) with E2A/PBX1, t(8;14)(q24;q32) and the immunoglobulin genes. Genetic changes associated with T ALL are also known, although their effect on outcome is less pronounced. Rare chromosomal abnormalities are continually being discovered in small patient subgroups leading to the identification of new ALL associated genetic changes. Alterations in chromosome number have a strong impact on outcome in childhood ALL. The association of a high hyperdiploid karyotype (51-65 chromosomes) with a good prognosis has been known for more than 20 years. Conversely, the loss of chromosomes in the near-haploid group (23-28 chromosomes) indicates a poor outcome. New methods of cancer classification involving gene expression profiling may eventually supercede cytogenetic analysis in the diagnosis and prediction of outcome in leukaemia. It is more likely that they will be used in a complementary approach alongside cytogenetic, FISH and molecular analysis to guide patient management in childhood ALL.

Adult↗
PubMed1997

Chromosomal abnormalities in cutaneous T-cell lymphoma and in its premalignant conditions as detected by G-banding and interphase cytogenetic methods.

The etiology of cutaneous T-cell lymphomas (CTCL) is unknown. We studied the pattern of chromosomal abnormalities with G-banding and interphase in situ hybridization methods in blood mononuclear cells in 17 patients representing the different phases of CTCL or the premalignant condition, parapsoriasis en plaque, and in 10 control persons. We used biotinylated centromere-specific probes with fluorescent detection (FISH) for chromosomes 1, 11, 8, and 17 and similar, enzymatically detectable, digoxigenin-labeled probes for chromosomes 1, 6, 12, 17, and 18. In G-banding, all patients showed numerical and structural chromosome aberrations. Numerical aberrations of chromosomes 6, 13, 15, and 17, marker chromosomes, and structural aberrations of chromosomes 3, 9, and 13 were increased in mycosis fungoides (MF) compared with healthy controls. In four of five patients the detection of a chromosomal clone preceded relapse or progression of the disease. In FISH of interphase cells, the cells abnormal for chromosomes 8 or 11, and for all four chromosomes collectively, were increased in MF and in Sezary Syndrome (SS). FISH and G-banding methods agreed statistically significantly for the detection of monosomy. Also, digoxigenin-labeled probes hybridized to interphases or mitoses detected aberrations corresponding to those observed with G-banding. Thus, chromosomally abnormal cells can be found in the peripheral blood of both parapsoriasis en plaque and CTCL patients. They can be detected with interphase cytogenetical methods, which obviates the need for dividing cells, often difficult to accomplish in CTCL.

Adult↗
PubMed1992

Chromosome abnormalities in human non-small cell lung cancer.

Clonal cytogenetic abnormalities found in 30 non-small cell lung carcinomas (NSCLC), including 28 newly diagnosed primary tumor specimens, are summarized. Multiple chromosome alterations were identified in every case, and 19 of 30 tumors had near-triploid or near-tetraploid karyotypes. Polysomy 7 and partial gains of 7p, including 7p11-p13 (site of the EGFR gene), were particularly frequent, occurring alone or in combination in 26 tumors. Recurrent losses involving 1p, 3p, 6q, 9p, 11p, 15p, and 17p (where the TP53 gene is located) were each seen in 16-25 cases. Five tumors exhibited double minutes, which were associated with amplified MYC1 (1 case) and EGFR (1 case), as determined by Southern analysis. The cytogenetic data were compiled from either short term cultures of tumor tissue harvested within 1-9 days (18 cases) or later harvests performed on long term cultures or cell lines (6 cases); in the other 6 cases results were obtained from both short term and long term cultures. Two studies were performed to validate the use of long term culture for cytogenetic analysis of solid lung tumors. First, in order to determine whether cytogenetic results from cultures are representative of the original tumor, the modal chromosome number of 13 specimens placed into culture was compared to the DNA index of the original tumor tissue, as measured by flow cytometry. The DNA indices of the solid tumor biopsies agreed with the degree of aneuploidy observed by cytogenetic analysis in every case. Second, in 6 cases we performed direct comparisons of karyotypes obtained from cells cultured by both methods. Identical chromosome abnormalities were detected in short term cultures and later harvests of the same specimen. Overall, our findings indicate that tumorigenesis in NSCLC is characterized by the accumulation of multiple chromosome alterations. Furthermore, these data demonstrate that recurrent cytogenetic changes can be identified in NSCLC and that detailed karyotypes from long term cultures are relevant to the original tumor. Chromosome abnormalities detected by these techniques may have clinical and biological significance. However, the complex pattern of karyotypic changes seen in newly diagnosed NSCLC emphasizes the need for future investigations of premalignant bronchial lesions in order to identify primary genetic changes important for early detection and intervention in this aggressive neoplasm.

Carcinoma, Non-Small-Cell Lung↗
PubMed1987

Chromosome abnormalities in Peyronie's disease.

Peyronie's disease is a localized and progressive fibrosis of unknown etiology that affects the tunica albuginea of the penis. We examined cytogenetically cell cultures derived from plaque, adjacent tunica, dermis and lymphocytes in patients with Peyronie's disease, and compared the results to cell cultures established from the tunica albuginea of control patients. Chromosomal abnormalities were detected in 9 plaque-derived cell cultures from 7 of 12 Peyronie's disease patients (58 per cent). Cells cultured from adjacent tunica, dermis and lymphocytes from the same patients were karyotypically normal, as were cultures derived from control (chordee and penile scar) patients. Chromosomal aberrations consisted of 5 numerical changes and 4 structural rearrangements, and included chromosomal additions (trisomy 7 and trisomy 8), deletions (45X,-Y), reciprocal translocations and inversions or markers. In 2 instances cultures derived from plaque tissue contained 2 independent chromosomal abnormalities. The apparently random chromosomal changes associated with Peyronie's disease suggests that karyotypic instability may be a common feature of cells within the plaque. It presently is unclear whether this finding represents multiple pathways for the development of Peyronie's disease or secondary consequences of Peyronie's disease.

Aged↗
PubMed1999

[Molecular cytogenetic pre- and postnatal diagnosis of chromosomal abnormalities].

Molecular cytogenetic studies in the prenatal and postnatal identification of chromosomal anomalies in children with mental retardation and congenital developmental malformations are discussed. Molecular cytogenetic techniques, such as fluorescence in situ hybridization (FISH) are employed after the use of classic cytogenetic studies. FISH diagnosis is recommended to apply in the cases when classic cytogenetic methods are not beneficial: post- and prenatal autosomal trisomies; gonosomal aneuploidies, including mosaic forms; marker chromosomes; structural chromosomal anomalies, including fragile X syndrome. The authors' experience showed that (1) FISH should be utilized only as an adjunctive test for classical cytogenetic studies when banding techniques are ineffective; (2) FISH confirms a cytogenetic diagnosis; (3) multicolored probe detection gives an additional possibility in the FISH analysis. The findings demonstrate that molecular cytogenetic methods provide a rapid accurate approach to investigating and diagnosing chromosomal anomalies. Molecular cytogenetic diagnosis allows a more correct correlation of chromosomal abnormalities to be shown with a clinical picture and assists in identifying new chromosomal syndromes in children with undifferentiated forms of mental retardation and congenital malformations.

Chromosome Aberrations↗
PubMed2003

Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q.

Various genomic alterations have been detected in glioblastoma. Chromosome 7p, with the epidermal growth factor receptor locus, together with chromosome 10q, with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent kinase inhibitor 2A locus, are among the most frequently damaged chromosomal regions in glioblastoma. In this study, we evaluated the genetic status of 32 glioblastomas by comparative genomic hybridization; the sensitivity of comparative genomic hybridization versus differential polymerase chain reaction to detect deletions at the phosphatase and tensin homologue deleted in chromosome 10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of genetic lesions (gain or loss) at 16 different selected loci (including oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13 different chromosomes; and the possible existence of a statistical association between any pair of molecular markers studied, to subdivide the glioblastoma entity molecularly. Comparative genomic hybridization showed that the most frequent region of gain was chromosome 7p, whereas the most frequent losses occurred on chromosomes 10q and 13q. The only statistically significant association was found for 7p gain and 10q loss.

Brain Neoplasms↗
PubMed2004

Identification and characterisation of constitutional chromosome abnormalities using arrays of bacterial artificial chromosomes.

Constitutional chromosome deletions and duplications frequently predispose to the development of a wide variety of cancers. We have developed a microarray of 6000 bacterial artificial chromosomes for array-based comparative genomic hybridisation, which provides an average resolution of 750 kb across the human genome. Using these arrays, subtle gains and losses of chromosome regions can be detected in constitutional cells, following a single overnight hybridisation. In this report, we demonstrate the efficiency of this procedure in identifying constitutional deletions and duplications associated with predisposition to retinoblastoma, Wilms tumour and Beckwith-Wiedemann syndrome.

Bacteria↗
PubMed2003

CGH and direct diagnosis of mosaic structural chromosomal abnormalities: description of a mosaic ring chromosome 17 and review of the literature.

We report the characterisation of a de novo supernumerary chromosome marker in a mosaic state (50%) by comparative genomic hybridisation (CGH) in an 8-year-old child with hypotonia, dysmorphia and mild-to-moderate mental retardation. We describe the combined use of CGH and fluorescence in situ hybridisation (FISH) to identify the origin of the additional chromosomal material. Visual analysis of 10 CGH-metaphase spreads revealed a gain of green fluorescent signal on pericentromeric region of chromosome 17. The CGH finding was confirmed by FISH analysis using a whole chromosome 17 paint, a chromosome 17 centromeric probe and the probe coding for the Smith-Magenis locus in 17p11.2. These results show that performing both CGH and FISH in combination with classical karyotyping will certainly allow the identification of imbalanced chromosome rearrangements and, by the way, allow the identification of genes involved in mental retardation and/or malformative pathology.

Child↗
PubMed1994

[Significance of chromosomal abnormalities in solid tumors of humans].

Solid tumours in man are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the tumour and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. Some primary abnormalities are so characteristic as to be virtually pathognomonic for particular types of solid tumours, eg, t (11;22)(q24;q12) in Ewing's sarcoma, t (9,22)(q22;q12) in extraskeletal myxoid chondrosarcoma, t (X;18)(p11;q11) in synovial sarcoma, and t (12;16)(q13;p11) in myxoid liposarcoma. To these purely cytogenetic data implicating specific genetic changes in carcinogenesis may now be added a growing evidence of molecular specificity emerging from recombinant DNA-studies. It appears that both currently known classes of directly cancer-relevant genes, the dominant oncogenes and the recessive tumour suppressor genes, are located at precisely those genomic sites that are visibly involved in neoplasia-associated chromosomal rearrangements. The importance of cytogenetic characterization of solid tumors is thus twofold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality identifies the presence of a neoplastic disease, and the specific type of aberration may reveal the true nature of the tumor and thus improve the diagnostic precision.

Chromosome Aberrations↗
PubMed1995

Analysis of chromosomal abnormalities in human sperm after chemotherapy by karyotyping and fluorescence in situ hybridization (FISH).

The frequency of numerical and structural chromosomal abnormalities was studied in the sperm of a lymphoma patient 3 years after MACOP-B chemotherapy (CT). Sperm karyotyping was performed by fusion of human sperm with hamster oocytes and analysis of 193 Q-banded sperm chromosomes. Multicolor fluorescence in situ hybridization (FISH) was performed on 10,228 sperm for analysis of disomy frequencies for chromosomes 1 and 12 and on 10,664 sperm for chromosomes X and Y. Sperm karyotyping demonstrated numerical abnormalities in 7.3% of the spreads, 6.7% hypohaploid and 0.5% hyperhaploid, giving a conservative estimate of aneuploidy of 1%. Structural chromosomal abnormalities were present in 7.3% of the karyotypes and 0.5% had both numerical and structural abnormalities. Results of FISH analyses yielded disomy frequencies of 0.10%, 0.11%, 0.04%, 0.05%, and 0.18% for chromosomes 1, 12, X, Y, and XY, respectively. The frequency of diploid sperm was 0.09%. The frequency of abnormalities was not significantly increased compared to control donors for any of the studies. Also, the frequencies of X- and Y-bearing sperm did not differ significantly from 50% in the sperm karyotyping or FISH studies.

Aneuploidy↗
PubMed1987

Chromosome abnormalities in malignant lymphoma in patients from Saitama.

Clonal chromosome abnormalities were found in 89 (97%) of 92 patients with non-Hodgkin's malignant lymphoma including immunologically determined 34 B- and 25 T-lymphomas; only 3 of 19 T-lymphoma patients examined had serum adult T-cell leukemia/lymphoma-associated antigen antibody. Association of 8q24 translocations with small non-cleaved cell (P less than 0.01) and that of t(14;18) (q32;q21) with follicular histology (P = 0.03) were significant. Several other abnormalities were also found to be correlated with histological or immunological phenotypes: trisomy 5 with diffuse, mixed cell lymphoma (P = 0.03); a break at 3q21 with diffuse, large cell lymphoma (P = 0.04); gain of chromosome 18 or X and rearrangements of 13q with immunoblastic lymphoma (P = 0.02, 0.03, and 0.03, respectively); and rearrangements of 7q with diffuse large cell histology (P = 0.02) and T-cell phenotype (P = 0.02). Multiple clones were more frequently seen in T-cell lymphoma than in B-cell lymphoma (P = 0.01). Structural changes of the long arm of chromosome 4 or 15 and a break in 6p21 were also associated with T-lymphoma (P = 0.03, respectively). Since the frequency of T-lymphoma is significantly higher and that of t(14;18) is significantly lower in the adult T-cell leukemia/lymphoma nonendemic area of Saitama in Japan than in Minnesota in the United States (P less than 0.01), factors affecting the lymphoma-genesis may be different or operating in different intensities in different areas.

Adolescent↗
PubMed1989

Chromosomal abnormalities and their correlations with asbestos exposure and survival in patients with mesothelioma.

Cytogenetic findings of our 30 previously reported and eight new patients with malignant pleural mesothelioma were summarised and correlated with asbestos fibre burden in lung tissue and survival. Successful cytogenetic analyses were performed on cells obtained from the tumours and/or pleural effusions of 34 of the 38 patients. Clonal chromosomal abnormalities were detected in 25 patients, 19 of them studied before treatment. Nine patients, seven of them studied before treatment, had normal karyotypes and/or non-clonal chromosomal abnormalities. Most of the karyotypic findings in the patients with clonal abnormalities were complex and heterogeneous, and no chromosome aberration specific to mesothelioma could be demonstrated. The following numerical abnormalities in decreasing order of frequency were preferentially present in karyotypic changes: -22, +7, -1, -3, -9, +11 and -14 (-/+ denoting partial or total loss or gain). Translocations and deletions involving a breakpoint at 1p11-p22 were the most frequent structural aberrations. Statistically significant correlations were found between high content of asbestos fibres in lung tissue and partial or total losses of chromosomes 1 and 4, and a breakpoint at 1p11-p22 (P = 0.0001, P = 0.003, P = 0.009, respectively). The number of copies of chromosome 7 short arms was inversely correlated with survival (P = 0.02). In this study no diagnostic cytogenetic markers of mesothelioma were found, instead the copy number of chromosome 7 short arms turned out to be a possible prognostic factor in malignant mesothelioma.

Adult↗
PubMed1982

The prevalence of chromosome abnormalities among mentally retarded persons in a geographically delimited area of Denmark.

A cytogenetic survey of an unselected group of mentally retarded persons in a geographically limited area was made in order to establish the frequency of chromosome abnormalities within this group. In the area there were 2,157 patients, both institutionalized and living at home. A chromosome analysis was performed in 1905 cases; 359 (18.8%) of these had a chromosome anomaly: 281 (14.7%) Down's syndrome, 45 (2.4%) autosomal anomaly other than Down's, and 33 (1.8%) sex chromosome anomaly. The frequency of chromosome aberrations in relation to the whole group was higher compared with similar surveys, which leads to the conclusion that the total number of mentally retarded persons living within a limited area is determined by many factors. This means that a comparison between frequencies of abnormal chromosomes in an unselected group of mentally retarded persons is only relevant when related to the whole population living in the investigation area.

Chromosome Aberrations↗