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At least 595 records · Page 33Linked to original sources
PubMed1998

Cytogenetic heterogeneity in a second primary radiation-induced bladder carcinoma: ten karyotypically unrelated clones.

Cytogenetic analysis of a transitional cell carcinoma (TCC) of the bladder, the tumor having developed 32 years after the patient received pelvic irradiation and interstitial radium implantation for an endometrial carcinoma, revealed the presence of 10 cytogenetically abnormal, unrelated clones. Although the tumor was poorly differentiated, all clones were pseudo- or near-diploid with rather simple balanced or unbalanced structural rearrangements or both. The chromosomes involved in structural changes more than once were chromosomes 8, 9, and 11, which were rearranged in three clones, and chromosomes 3 and 17, both rearranged in two clones. No previous TCC of the bladder with cytogenetically unrelated clones has been reported, nor has any such radiation-induced tumor with chromosomal abnormalities been described. The distinct karyotypic and clonal pattern of the case presented here is probably indicative of a carcinogenic field effect due to the previous pelvic irradiation. Postradiation bladder carcinomas thus seem to be distinct cytogenetically in addition to their known unique etiological and clinical features.

Aged↗
PubMed1998

Clear-cell and papillary carcinoma of the kidney: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification, cytogenetics, and fluorescence in situ hybridization.

Clear-cell and papillary renal cell carcinomas (RCCs) have specific genetic changes that allow them to be classified on the basis of histopathology and on the basis of cytogenetic and molecular genetic findings. Clear-cell carcinomas are characterized by a deletion of gene sequences on the short arm of chromosome 3 (3p). Papillary RCCs do not have 3p deletions but have an increase in chromosomal number that usually includes trisomies of chromosomes 7 and 17. This study was undertaken to determine whether PCR-amplified DNA microsatellites can be used to detect numerical abnormalities of chromosomes 7 and 17 and whether the numerical abnormalities and 3p deletions that are detected by microsatellite analysis can be correlated with histopathologic tumor types. A series of histologically unambiguous RCCs consisting of three papillary and ten clear-cell RCCs were studied by cytogenetics and by fluorescence in situ hybridization (FISH) with chromosome 7 and 17 centromeric probes. Microsatellites on the long and short arms of chromosomes 3, 7, and 17 were amplified in paired normal tissue and tumor samples, and the reaction products were analyzed for differences between the normal and the tumor allele ratios. Clear-cell carcinomas showed loss of heterozygosity (LOH) of 3p but not 3q alleles in eight of ten cases. LOH of 3p and 3q was seen in one case of papillary RCC that cytogenetically had two normal chromosomes 3. This indicated a nondisjunction duplication that could be confused with monosomy 3 if only microsatellite studies were performed. Differences in microsatellite allele ratios between normal tissue and tumor correlated with the presence of trisomy 7 that was identified in clear-cell and papillary RCCs by cytogenetics and by FISH. Microsatellite analysis did not detect numerical chromosome 17 abnormalities in the papillary RCCs but did show an abnormality in one clear-cell carcinoma that was markedly aneusomic for chromosomes 7 and 17 by FISH. In this collection of cases, microsatellite amplification genetically distinguished only clear-cell RCCs showing 3p but not 3q LOH as a separate class of tumors. The method detected abnormalities in chromosome number that were found in both clear-cell and papillary RCCs.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Monitoring of molecular and cytogenetic damage in lymphocytes from three persons with polycystic kidney disease.

BACKGROUND: Much interest has been generated in the studies that would help to understand whether there is a causal association between disease and various types of molecular or cytogenetic damage detected in human cells. MATERIALS AND METHODS: The aims of this study were to elicit the possible association between DNA and cytogenetic damage induced in lymphocytes of three members of a family with autosomal dominant polycystic kidney disease (ADPKD). The predictability to develop cancer or to sensitive response to environmental exposure of the young girl at the age of 19, her brother (9 years old) and a maternal aunt at the age of 41 were sought. Cytogenetic studies, analysis of DNA damage by single cell gel electrophoresis assay (SCGE known as a Comet assay), and analysis of p21ras protein level in blood plasma were carried out on their lymphocytes. RESULTS: The analysis for presence of chromosome aberrations in the first mitosis and sister chromatid exchanges in the second mitosis revealed elevated levels of cytogenetic biomarkers when compared to the mean values observed in the reference group in environmental biological monitoring studies. Results of sister chromatid exchanges (SCE) and percent of cells with elevated number of exchanges (high frequency cells) that were significantly higher in two probands had demonstrated susceptibility to or possibility of environmental exposure (pesticides, smoking). The results of this study show that the lymphocytes of two persons revealed increased sensitivity to 0.5 Gy dose of gamma radiation expressed in the increased, although statistically insignificant, damage detected on the molecular level after cell irradiation. CONCLUSIONS: The latter might be associated with a specific aberration present in the cells of these persons. But final conclusions can be arrived at when an application of FISH technique is completed.

Adolescent↗
PubMed2000

Novel molecular cytogenetic techniques for identifying complex chromosomal rearrangements: technology and applications in molecular medicine.

Molecular cytogenetic techniques that are based on fluorescence in situ hybridisation (FISH) have become invaluable tools for the diagnosis and identification of the numerous chromosomal aberrations that are associated with neoplastic disease, including both haematological malignancies and solid tumours. FISH can be used to identify chromosomal rearrangements, by detecting specific DNA sequences with fluorescently labelled DNA probes. The technique of comparative genomic hybridisation (CGH) involves two-colour FISH. It can be used to establish ratios of fluorescence intensity values between tumour DNA and control DNA along normal reference metaphase chromosomes, and thereby to detect DNA copy-number changes such as gains and losses of specific chromosomal regions and gene amplifications. Spectral karyotyping (SKY) is a novel molecular cytogenetic method for characterising numerical and structural chromosomal aberrations. SKY involves the simultaneous hybridisation of 24 differentially labelled chromosome-painting probes, followed by spectral imaging and chromosome classification, and produces a colour karyotype of the entire genome. The use of SKY has contributed significantly to the identification of chromosomal anomalies that are associated with constitutional and cancer cytogenetics, and has revealed many aberrations that go undetected by traditional banding techniques. In this article, we have reviewed these new molecular cytogenetic techniques and described their various applications in molecular medicine.

Journal Article↗
PubMed1998

Molecular cytogenetic studies of pediatric ependymomas.

Cytogenetic and molecular studies of ependymomas have previously demonstrated deletions of chromosomes 17 and 22 as frequent abnormalities, implicating inactivation of tumor suppressor genes in the pathogenesis of these tumors. In the present study, we analyzed 22 childhood ependymomas by standard cytogenetic analysis, fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)-based microsatellite analysis of chromosomes 17 and 22. Microsatellite analysis of chromosome 6 was performed to identify submicroscopic deletions implicated by the cytogenetic studies. Among the 22 cases, we demonstrated loss of chromosome 22 in 2 patients, deletion of chromosome 17 in 2 patients, and rearrangements or deletions of chromosome 6 in 5 patients. These data do not suggest that loss of a gene on chromosome 17p plays a primary role in the initiation of pediatric ependymomas. This is in contrast to what has been reported for pediatric CNS primitive neuroectodermal tumors and malignant astrocytomas, in which deletion of 17p is regarded as a primary event. Furthermore, loss of chromosome 22 may define a subset of ependymomas more commonly seen in adults. Cytogenetic studies in this series, however, suggest that a region on the long arm of chromosome may be involved in the development and/or progression of ependymomas in children.

Adolescent↗
PubMed2002

Y-chromosome microdeletions and cytogenetic findings in unselected ICSI candidates at a Danish fertility clinic.

PURPOSE: To determine the frequency and type of microdeletions on the Y chromosome, and to evaluate cytogenetic findings in unselected ICSI candidates at a Danish Fertility Clinic. METHODS: Genomic DNA was extracted from blood samples, which were collected prospectively from 400 ICSI candidates attending the Fertility Clinic at Aarhus University Hospital, Denmark. Twenty-five sequence tagged sites (STSs) spanning the azoospermia factor (AZF) regions of the Y chromosome were amplified in 5 multiplex sets to investigate Y microdeletions. Semen analysis, karyotype analysis, and histological evaluation of testicular biopsies were also performed. RESULTS: Y microdeletions were detected in 3 (0.75%) of 400 unselected ICSI candidates. The frequency of Y microdeletions was found higher in azoospermic men (2%) than in oligozoospermic men (0.6%). Two patients having oligozoospermia had Y microdeletions in the AZFc region only, whereas the patient having azoospermia had Y microdeletions spanning the AZFb and AZFc regions. No microdeletion was detected in the AZFa region. Chromosomal anomalies were found in 6.1% of azoospermic men and in 2.7% of oligozoospermic men. A high frequency of cytogenetic abnormalities was found in normozoospermic men with fertilization failure (7.4%). CONCLUSIONS: The frequency of Y microdeletions both in the unselected ICSI candidates and subgroups classified as azoospermic and oligozoospermic seems rather low compared to results of previous studies, which have been quite varying. It is possible that in addition to patient selection criteria, ethnical and geographical differences may contribute to these variations. Cytogenetic evaluation of normozoospermic men with fertilization failure seems indicated because of a high frequency of cytogenetic abnormalities.

Adult↗
PubMed2000

Cytogenetic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leukemias.

Between 1977 and 1996, cytogenetic investigations were performed on 182 childhood (< or = 16 yr) acute lymphoblastic leukemias (ALL), constituting 94% (182 of 194) of all ALL patients diagnosed and treated at the Departments of Pediatrics, Lund and Malmo University Hospitals, Sweden, during these two decades. The cytogenetic analyses were successful in 152 cases (84%). The failure rate was higher for the ALL investigated before 1987 (30% vs. 4%, p < 0.0001), and also the incidence of cytogenetically normal cases was higher during 1977-86 (43% vs. 25%, p < 0.05). Clonal chromosomal abnormalities were found in 103 (68%) ALL. Structural rearrangements were detected, by chromosome banding alone, in 76 cases (50%). Fluorescence in situ hybridization (FISH) was used to identify cases with t(12;21), 11q23 rearrangements, and 9p deletions, using probes for ETV6/CBFA2, MLL, and CDKN2A/B, in 72 cases from which cells in fixative and/or unstained metaphase preparations were available. In total, the most common structural rearrangements were del(9p) (17%), t(12;21) (15%), del(6q) (8%), and MLL rearrangements (4%). Six (32%) of nineteen cytogenetically normal ALL analyzed by FISH harbored cryptic abnormalities; three displayed t(12;21) and four had del(9p), one of which also carried a t(12;21). Five (45%) of the t(12;21)-positive ALL showed +der(21)t(12;21) or ider(21)(q10)t(12;21), resulting in the formation of double fusion genes. Among the more rare aberrations, eight structural rearrangements were identified as novel recurrent ALL-associated abnormalities, and nine cases harbored rearrangements previously not reported. Sixteen cases displayed karyotypically unrelated clones at different investigations. Seven ALL (5%) showed simple chromosomal changes, unrelated to the aberrations detected at diagnosis, during morphologic and clinical remission, and in all but one instance the patients remained in remission, with the abnormal clone disappearing in subsequent investigations. This indicates that the emergence of novel clonal chromosomal aberrations during remission in childhood ALL is rather common and does not by necessity predict a forthcoming relapse.

Adolescent↗
PubMed2002

Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation.

Relatively little is known about the cytogenetic features of multiple myeloma (MM) when compared to other hematologic malignancies. The reasons for this are most likely manifold, and include a low mitotic index of the malignant cells and the presence of cytogenetically cryptic abnormalities as well as of complex karyotypes with poor chromosome morphology. In the present study, we have investigated whether various culture conditions may influence the yield of abnormal metaphases in MM and, in the related plasma cell dyscrasias, monoclonal gammopathy of undetermined significance (MGUS) and plasmacytomas (PC). In addition, the possible impact of age, gender, and disease phase on the cytogenetic features has been analyzed. A total of 95 samples from 74 cases (68 MM, three PC, and three MGUS patients) were obtained for cytogenetic analysis. The samples were cultured either in conventional medium or in medium containing IL-6 and GM-CSF, and the culture times varied from 24 to 120 h. In total, 186 cultures were analyzed. Metaphase fluorescence in situ hybridization analysis using probes specific for 14q32, i.e. IGH rearrangements, could be performed in 57 of the 74 cases, and revealed 14q32 aberrations in 10 cases not seen by conventional G-banding. Abnormal karyotypes were detected in 77 (41%) of the 186 cultures, 46 (48%) of the 95 samples, and in 41 (55%) of the 74 patients, revealing a total of 20 chromosomal aberrations previously not reported in plasma cell dyscrasias. We found no evidence that gender, age, disease phase, culture time, or cytokine stimulation significantly influences the karyotypic features of MM.

Adult↗
PubMed1983

Cytogenetic analysis of leukaemic colonies from acute and chronic myelogenous leukaemia.

We have utilized the blast cell assay of Buick et al. (1977) to grow and subsequently cytogenetically analyze cultured colony forming cells (CFUs) from patients with acute and chronic myelogenous leukaemia (AML, CML). Cytogenetic analysis of CFUs was successful in 30/36 cases (83%), a success rate similar to direct harvesting techniques. Identical clonal chromosomal abnormalities demonstrated by direct techniques were also observed in CFUs from AML and CML. Removal of T-precursor cells by E-rosetting prior to plating did not eliminate growth of karyotypically normal cells. The combination of morphologic and cytogenetic studies performed clearly established that the assay system supports the growth of leukaemic progenitors. Although both karyotypically normal and abnormal leukaemic colonies grew in this assay, growth of leukaemic colonies was much more likely if the plated cells were karyotypically abnormal (P = 0.010). Leukaemic colony growth was also more frequent if the tritiated thymidine labelling index (LI%) of plated cells was greater than or equal to 5% (P = 0.018). Leukaemic colonies were most likely (P = 0.018) to have been derived from plated cells with both abnormal karyotype and high LI% (greater than or equal to 5%). Cytogenetic analyses from cultured cells revealed only those karyotypic features found in the uncultured cells (i.e., no additional abnormal sublines were found). However, in most cases, the greatly enhanced number and quality of mitotic figures allowed for more detailed banding analysis.

Adolescent↗
PubMed1994

Cytogenetic analysis of multifocal breast carcinomas: detection of karyotypically unrelated clones as well as clonal similarities between tumour foci.

Cytogenetic analysis was performed on short-term cell cultures of two foci (A and B) from each of three multifocal breast carcinomas. In case I, four clones (three related and one unrelated) were detected in sample A. In sample B, two of the three related clones and the unrelated clone seen in A were found, as was also a third subclone showing a pattern of clonal evolution slightly different from that detected in A. In cases II and III, multiple cytogenetically unrelated clones were found in A and B, with only one clone being shared by both foci in each case. Our finding of cytogenetic similarities between macroscopically distinct tumour lesions indicates that the multifocality reflects intramammary tumour spread rather than the synchronous emergence of pathogenetically independent carcinomas within the same breast. On the other hand, the detection of karyotypic heterogeneity in the form of cytogenetically unrelated clones in all foci suggests that human breast carcinoma may be polyclonal. This polyclonality may be part of the explanation for the cellular heterogeneity commonly seen at the phenotypic level in breast cancer.

Aged↗
PubMed2000

Sjögren's syndrome and MALT lymphomas of salivary glands: a DNA-cytometric and interphase-cytogenetic study.

Few and conflicting cytogenetic data are available concerning the chromosomal constitution of (mainly gastric) extranodal marginal zone B-cell non-Hodgkin's lymphoma arising from mucosa-associated lymphoid tissue (MALT)-type lymphoma. The majority of salivary gland MALT lymphomas are thought to develop from longstanding Sjögren's syndrome/benign lymphoepithelial lesion (BLEL). We tried to achieve a better comprehension of related cytogenetic alterations by comparing DNA-ploidy and numerical chromosomal (#) aberrations, assessed by different techniques of DNA cytometry (image cytometry) and interphase cytogenetics using nonradiographic in situ hybridization (centromere specific probes for #3, 7, 12, 18) on 12 cases of BLEL, 13 low-grade MALT lymphomas (LG-MALT-L) and 4 high-grade MALT lymphomas (HG-MALT-L) of salivary gland. Both techniques were applied on tissue sections preferentially, enabling a reliable measurement of histomorphologically identified areas. No case of BLEL showed cytogenetic abnormalities. Three of 4 HG- and 2 of 13 LG-MALT-L exhibited complex chromosomal gains in nonisotopic in situ hybridization, which were reflected by DNA nondiploidy in image cytometry. In 6 of 13 LG- and lof 4 HG-MALT-L, one or two numerical chromosomal aberrations were demonstrated by nonisotopic in situ hybridization, which could not be resolved by image cytometry. In the 11 DNA-diploid LG-MALT-L, trisomies 18, 3, and 12 were found in 36, 12, and 9%, respectively. In conclusion, comparing BLEL, which showed no chromosomal aberrations, with LG- and HG-MALT-L, an increase in frequency and number of numerical aberrations and DNA nondiploidy was seen. Peritetraploid DNA nondiploidy might be characteristic for HG-MALT-L of salivary gland as it is a rare finding in MALT lymphomas of other sites. It is unclear whether the documented chromosomal aberrations in LG-MALT-L, especially increased rate of trisomy 18, indicate a pathogenic impact or merely reflect genetic instability.

Adult↗
PubMed2000

Quantification of BCR-ABL transcripts in CML patients in cytogenetic remission after interferon-alpha-based therapy.

We measured using a competitive quantitative polymerase chain reaction-capillary electrophoresis (PCR-CE)-based assay, the levels of bcr-abl transcripts in 44 patients with chronic myeloid leukemia (CML) after interferon-alpha (IFN-alpha) therapy, who achieved a major (10 patients, MCR group) or complete (34 patients, CCR group) cytogenetic response. All 34 CCR patients had molecular evidence of residual disease detected in bone marrow samples at the time of best karyotypic response. The median number of bcr-abl transcripts of 34 evaluable patients in the CCR group at the time of complete cytogenetic remission was 4/microg RNA (range 3-4600), while the median number of bcr-abl transcripts of 10 patients in the MCR group at the time of best cytogenetic response was 4490/microg RNA (range 600-23 900) (P = 0.000024). In nine CCR and five MCR patients we were able to quantify the amount of bcr-abl transcript both at diagnosis and after interferon therapy: no statistical difference (P = 0.18) was found between the two groups at diagnosis (median bcr-abl transcripts/microg RNA was 30 000 vs. 39 650, respectively). During IFN-alpha therapy, the two groups were evaluable at the time of major karyotypic conversion: at this point, there was a statistical difference of expression of bcr-abl transcript between the CCR group (17 patients) (median 2700; range 76-40 000) and the MCR group (10 patients) (median 4490; range 600-23 900), respectively (P = 0.046). No differences of bcr-abl amount of transcript were found in patients with CCR obtained either by IFN-alpha therapy alone (20 patients) vs. IFN-alpha plus ABMT (13 patients) (P = 0.47). We firstly demonstrated that although the CCR and MCR groups were clinically, cytogenetically and molecularly indistinguishable at diagnosis, the two groups could be recognized successfully during interferon therapy based on the level of bcr-abl transcript.

Adolescent↗
PubMed2006

Clonal cytogenetic changes and myeloma relapse after reduced intensity conditioning allogeneic transplantation.

To identify a correlation between metaphase cytogenetics and relapse after reduced intensity conditioning (RIC) allotransplant for patients with multiple myeloma, data on 60 patients (median age 52) who received grafts from a sibling (n = 49) or unrelated donor (n = 11) were analyzed. Fifty-three patients (88%) showed chromosomal abnormalities (CA) before the allotransplant, including 42 with abnormalities involving 13q (CA13). Twenty-two patients (41%) relapsed post-allotransplant at a median of 165 days. Of these, 11 patients showed abnormal cytogenetics at the time of post-allotransplant relapse at a median of 167 days. Of 54 patients who developed graft-versus-host disease, relapse occurred in 19 of 48 patients (43%) with CA present before RCI allotransplant, versus 1 of 6 without CA (17%) (P = 0.06). Loss of CA before RIC allotransplant and disease status > PR after RIC allotransplant were significantly associated with a lower risk of post-allotransplant relapse with cytogenetic abnormalities; 5.2 vs 36%, and 18 vs 53%, (both P < 0.05), respectively. The current data suggests that myeloma associated with persistent clonal cytogenetic abnormalities is an entity which most likely escapes the effects of a graft versus myeloma activity, maybe because of acquisition of resistance to immunologic manipulations.

Adult↗
PubMed1997

Cytogenetically aberrant cells are present in the CD34+CD33-38-19- marrow compartment in children with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL), the most common cancer in childhood, is characterized by clonal proliferation of transformed lymphoblasts that comprise the majority of marrow and/or blood specimens. Although the leukemic cells typically express antigens associated with lymphoid maturation or activation (ie CD19, CD38, etc), it has been suggested that ALL blasts may evolve from a more primitive precursor. Increased understanding of the phenotypic and molecular heterogeneity of cells in ALL may provide clues to leukemogenesis and/ or impact prognostication or treatment. We utilized a phenotype/genotype approach to measure the prevalence and frequency of cytogenetically aberrant cells in a phenotypically defined primitive compartment (CD34+33-19-38-; CD34+Lin-). Bone marrow cells were flow cytometrically sorted into CD34-Lin+, CD34+Lin+ and CD34+Lin- subpopulations. Fluorescence in situ hybridization (FISH) was used to quantify the frequency of cells with aneusomies in the sorted populations. Approximately 26% (5/19) of ALL cases at diagnosis contain cytogenetically aberrant CD34+Lin- cells. The frequency of cytogenetically aberrant cells in the CD34+Lin- compartment is independent of FAB, WBC and blast counts. These data indicate that cytogenetically aberrant cells may reside in a phenotypically defined primitive subpopulation and suggest that ALL blasts in some patients may evolve from a precursor compartment.

ADP-ribosyl Cyclase↗
PubMed2001

Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity and response to GM-CSF.

The current study was undertaken to search for differences in the biology of cytogenetic subgroups in patients with de novo acute myeloid leukemia (AML). In addition, factors influencing the metabolism of cytosine arabinoside (araC) as the key agent of antileukemic activity were assessed. Bone marrow aspirates from 91 patients with newly diagnosed AML in whom karyotypes were successfully obtained were analyzed: (1) for spontaneous proliferative activity by 3H-thymidine (3H-TdR) incorporation; (2) proliferative response to GM-CSF by in vitro incubation of blasts for 48 h with or without GM-CSF (100 U/ml) followed by an additional 4-h exposure to 3H-TdR (0.5 microCi/ml); and (3) parameters of araC metabolism comprising 3H-araC uptake in vitro and the activities of polymerase alpha (poly alpha), deoxycytidine kinase (DCK) and deoxycytidine deaminase (DCD). According to the results of chromosome analyses four cytogenetic subgroups were discriminated: (I) normal karyotypes (n = 38); (II) favorable karyotypes [t8;21), t(15;17), inv(16)] (n = 16); (III) unfavorable karyotypes [inv (3), -5, 5q-, t(6;9), +8, t (9;11), complex abnormalities] (n = 20); (IV) karyotypes of unknown prognostic significance (n = 17). Proliferative activity of leukemic blasts was significantly higher in favorable karyotypes (group II) as compared to cases with unfavorable cytogenetics (group III) with median values and range for 3H-TdR uptake in group II of 2.48 pmol/10(5) cells (0.28-25.8) and in group III of 0.51 pmol/10(5) cells (0.04-7.6) (P = 0.0096). The respective values in group I and group IV were 0.7pmol/10(5) cells (0.0-6.7) and 0.98 pmol/10(5) cells (0.0-4.0), respectively. Inversely, response to GM-CSF, as defined by an increase in 3H-TdR incorporation >1.5- fold over control values after 48h of GM-CSF exposure, was significantly lower for patients with a favorable karyotype (group II) as compared to group I (P = 0.04) and group III (P = 0.013). No significant differences between karyotype groups I, II, III and IV were found for 3H-araC incorporation, nor for the activities of poly alpha, DCK and DCD. These data demonstrate differences in the biology of cytogenetic subgroups in AML which may partly explain the well established differences in clinical outcome.

Acute Disease↗
PubMed2006

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma.

In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (Delta13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n=794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if Delta13, p53 deletion or t(4;14) was present, but only Delta13 remained significant on multivariate analysis. Patients with Delta13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with Delta13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable Delta13 disappeared; their outcome matched that of patients with no detectable Delta13 (P=0.115). Addition of ploidy status to iFISH-Delta13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH Delta13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with Delta13. We conclude that Delta13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of Delta13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.

Adult↗
PubMed2006

Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism.

The identification of the candidate genes for autism through linkage and association studies has proven to be a difficult enterprise. An alternative approach is the analysis of cytogenetic abnormalities associated with autism. We present a review of all studies to date that relate patients with cytogenetic abnormalities to the autism phenotype. A literature survey of the Medline and Pubmed databases was performed, using multiple keyword searches. Additional searches through cited references and abstracts from the major genetic conferences from 2000 onwards completed the search. The quality of the phenotype (i.e. of the autism spectrum diagnosis) was rated for each included case. Available specific probe and marker information was used to define optimally the boundaries of the cytogenetic abnormalities. In case of recurrent deletions or duplications on chromosome 15 and 22, the positions of the low copy repeats that are thought to mediate these rearrangements were used to define the most likely boundaries of the implicated 'Cytogenetic Regions Of Interest' (CROIs). If no molecular data were available, the sequence position of the relevant chromosome bands was used to obtain the approximate molecular boundaries of the CROI. The findings of the current review indicate: (1) several regions of overlap between CROIs and known loci of significant linkage and/or association findings, and (2) additional regions of overlap among multiple CROIs at the same locus. Whereas the first finding confirms previous linkage/association findings, the latter may represent novel, not previously identified regions containing genes that contribute to autism. This analysis not only has confirmed the presence of several known autism risk regions but has also revealed additional previously unidentified loci, including 2q37, 5p15, 11q25, 16q22.3, 17p11.2, 18q21.1, 18q23, 22q11.2, 22q13.3 and Xp22.2-p22.3.

Autistic Disorder↗
PubMed1996

Cytogenetic clonality analysis: typical patterns in myelodysplastic syndrome and acute myeloid leukaemia.

The cell morphology and karyotype of bone marrow samples from 24 patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) were studied simultaneously with a combined technique of May-Grünwald-Giemsa (MGG) staining and fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes. This enabled us to investigate cell lineage involvement in three malignant conditions: MDS (n = 12), leukaemia-transformed MDS (LT-MDS) (n = 5) and de novo AML (n = 7). In MDS we found blasts and often significant proportions of mature granulocytic and erythroid cells to be cytogenetically abnormal. Percentages of granulocytic and erythroid cells with cytogenetic aberrations were generally less than those of blasts. These data support the involvement of a transformed pluripotent stem cell that has retained maturation abilities. In two patients with chronic myelomonocytic leukaemia (CMMoL) the clonal involvement of monocytes was predominant. Results in the five patients with LT-MDS were similar to those in MDS. In the bone marrow of five of the seven de novo AML patients the cytogenetic abnormalities were restricted to the blasts and did not include the more mature granulocytic or erythroid populations. In the other two patients with AML, both with a t(8;21) and a loss of the Y chromosome, high percentages of mature neutrophils were cytogenetically abnormal. These patterns of clonal lineage involvement in MDS, LT-MDS, t(8;21) AML and AML appear typical and may be of clinical use, for example, for distinguishing LT-MDS from de novo AML in newly presenting patients.

Acute Disease↗