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PubMed1992

High-resolution cytogenetic-based physical map of human chromosome 16.

A panel of 54 mouse/human somatic cell hybrids, each possessing various portions of chromosome 16, was constructed; 46 were constructed from naturally occurring rearrangements of this chromosome, which were ascertained in clinical cytogenetics laboratories, and a further 8 from rearrangements spontaneously arising during tissue culture. By mapping 235 DNA markers to this panel of hybrids, and in relation to four fragile sites and the centromere, a cytogenetic-based physical map of chromosome 16 with an average resolution of 1.6 Mb was generated. Included are 66 DNA markers that have been typed in the CEPH pedigrees, and these will allow the construction of a detailed correlation of the cytogenetic-based physical map and the genetic map of this chromosome. Cosmids from chromosome 16 that have been assembled into contigs by use of repetitive sequence fingerprinting have been mapped to the hybrid panel. Approximately 11% of the euchromatin is now both represented in such contigs and located on the cytogenetic-based physical map. This high-resolution cytogenetic-based physical map of chromosome 16 will provide the basis for the cloning of genetically mapped disease genes, genes disrupted in cytogenetic rearrangements that have produced abnormal phenotypes, and cancer breakpoints.

Animals↗
PubMed2005

Cytogenetic aspects of adult primary myelodysplastic syndromes: clinical implications.

Myelodysplastic syndrome (MDS) is a heterogeneous disease from the clinical, biological and morphological point of view. The pathogenesis of MDS is not well established and it appears to occur complex changes in the stem cell biology. Clonal chromosomal aberrations are found in 30-50% of primary MDS and no specific cytogenetic abnormality has as yet been defined. The chromosomal abnormalities are predominantly characterized by partial/total chromosomal losses or chromosomal gains. These chromosomal abnormalities include mainly -5/del(5q), -7/del(7q), del(11q), del(12p), del(20q), -Y, and +8. The role of cytogenetic analysis in the diagnosis, prognosis, taking treatment decisions and follow up of patients with MDS has been clearly defined. Despite its difficulties in obtaining for analysis high quality metaphases conventional cytogenetics continues to be the basic technique for cytogenetic evaluation of a MDS patient. Other molecular cytogenetic methods have been shown to be complementary, without replacing the information obtained with this technique. Further investigations with both conventional and molecular cytogenetics in relation to clinical features as well as other molecular methods will undoubtedly contribute to improve understanding of the underlying genetic events responsible for the development and evolution of MDS leading to more accurate classification and management of MDS patients.

Animals↗
PubMed1999

P-glycoprotein and terminal transferase expression identify prognostic subsets within cytogenetic risk classes in acute myeloid leukemia.

Clinical and biological features were assessed in 204 consecutive de novo adult acute myeloid leukemia (AML) patients who received intensive chemotherapy regimens. Multiparameter flow cytometric assays both of the multidrug resistance (MDR-1)-associated P-glycoprotein (PGP) using the UIC2 monoclonal antibody (MoAb), and of terminal transferase (TdT) were performed. Cytogenetic findings were obtained from 196 patients with high resolution banding. At onset, UIC2 and TdT positivities were detected in 58.5% and 24% of cases, respectively. There were strict correlations either between UIC2 negativity and FAB M3 or between TdT and FAB M0-M1 (P = 0.001 and < 0.0001, respectively). On the other hand, age was significantly associated with cytogenetic risk classes (P < 0.0001). CD34 positivity was highly correlated with TdT expression (P < 0.0001). Moreover, CD7 and CD11b were significantly represented in UIC2+ subset (P < 0.0001). Rhodamine 123 (Rh 123) efflux was significantly higher in 75 UIC2 positive patients compared to 65 UIC2 negative ones (P < 0.001). As regards to cytogenetics, TdT positivity was strongly related either to t(9;22) or single/associated anomalies of chromosome 7; on the other hand, most or all cases with t(8;21) or t(15;17) were UIC2 or TdT negative, respectively. The rate of first complete remission (CR) differed both between UIC2+ and UIC2- cases and between TdT+ and TdT- ones (40% versus 72%, P < 0.001; and 36% versus 61%, P = 0.001, respectively). The survival rates (Kaplan-Meier method) were significantly shorter either in UIC2+ or in TdT+ patients (P = 0.005 and = 0.011, respectively). UIC2 and TdT negative cases showed longer remission duration (P = 0.03 and = 0.22, respectively). The additional effect of UIC2 and TdT on prognosis allowed us to identify two subsets of patients, the first [UIC2- TdT-] at better and the second [UIC2+ TdT+] at worse clinical outcome compared to single UIC2 and TdT cases, concerning CR (P < 0.001), survival (P < 0.0001) and CR duration (P = 0.007). The combinations [UIC2+ TdT-] and [UIC2- TdT+] showed an intermediate clinical course. A strong difference was found between poor risk and intermediate/favorable risk cytogenetic classes with regard to CR rate (P < 0.0001), overall survival and CR duration (P < 0.001). Nevertheless, within the poor risk class, UIC2 positivity was able to identify patients at worst prognosis with regard to CR (P = 0.005), survival (P = 0.02) and CR duration (P = 0.015). On the other hand, UIC2 and TdT negativity allowed us to distinguish patients with longer survival (P = 0.012 and = 0.04, respectively) and CR duration (P = 0.04 and = 0.025, respectively) within the intermediate/favorable risk class. The independent prognostic value of UIC2, TdT and cytogenetic risk classes was confirmed in multivariate analysis. These results suggest that PGP and TdT expressions, together with cytogenetic findings, may represent a basic predictor of chemotherapeutic failure in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Cytogenetic abnormalities during clinical, immunophenotypic, and molecular remission in pediatric acute lymphoblastic leukemia.

The significance of random cytogenetic abnormalities detected in pediatric acute lymphoblastic leukemia (ALL) during remission is unknown. We studied 10 of 72 consecutive ALL patients who developed cytogenetic abnormalities during clinical remission to determine their effect on remission status. The cytogenetic abnormalities occurred at a median of 14.5 months (range 5-72) from the initial diagnosis. Five abnormalities were designated as clonal (monosomy 21 in three metaphases and 64 approximately 69,XXY in three metaphases from one patient at different times, and del(20)(q12q13) in three metaphases, add(13)(q34) in two metaphases, and ?del(19)(p11) in two metaphases from three different patients). Seven abnormalities were previously described: del(5)(q12), del(5)(q33), -7, del(11)(q23), +12, and +13 each in one metaphase, and del(20)(q12q13) in three metaphases). The remaining cytogenetic abnormalities were nonclonal and random. Flow cytometry and analysis of IgH and TcR gene rearrangements showed that all evaluable patients were in immunophenotypic and molecular remission, respectively. Eight patients remain in clinical and molecular remission a median of 9 months (range 7-18) after detecting the cytogenetic abnormality, and the leukemia in two patients has relapsed. During remission, cytogenetic abnormalities may not be a harbinger of leukemia relapse in pediatric ALL; therefore, a wait-and-see approach is prudent.

Aneuploidy↗
PubMed1995

[Correlation between sensitivity of the cytogenetic and cytological analysis and thoracoscopic findings in the study of malignant pleural effusions].

We studied 104 patients with pleural effusion. All underwent thoracoscopic exploration to allow direct examination of any pleural lesions present. At the same time pleural biopsies for histopathologic study and samples of pleural fluid for cytopathologic and cytogenetic study were taken. The volume of fluid in pleural cavity was also measured. The aims of the study were: a) to evaluate the sensitivity of cytogenetic analysis and cytopathology, both separately and together, and b) to look for a correlation between the sensitivity of these cell studies and the following thoracoscopic findings: tissue biopsy of pleural neoplasms, volume of pleural effusion and extension of neoplastic lesions in the pleural cavity. Seventeen of the pleural liquids studied were benign and 87 were neoplastic. Cytopathology was sensitive in 55% of the neoplastic cases and cytogenetic study was sensitive in 49%. Sensitivity rose to 74% when both techniques were applied. Cytogenetic study yielded a higher percentage of correct diagnoses in the group with hematologic neoplasia, whereas cytopathology was correct more often in cases of solid tumors, though these differences were not statistically significant. Use of both techniques resulted in correct diagnosis in 92% of patients with mesotheliomas. The number or correct diagnoses achieved with cytopathology tended to increase with size of macroscopic pleural lesion whereas cytogenetic study was more sensitive in patients with minimal or incipient pleural involvement. There were no statistically significant differences in sensitivity of cytopathology and cytogenetic analysis with regard to volume of pleural effusion.

Adolescent↗
PubMed2000

Cytogenetic response to autografting in chronic myelogenous leukemia correlates with the amount of BCR-ABL positive cells in the graft.

OBJECTIVE: An important step in successful autografting of patients with chronic myelogenous leukemia is the delivery of a leukemia-free graft. We conducted this study to determine whether the cytogenetic response after autografting was correlated with the number of BCR ABL-positive cells present within the stem cell grafts. MATERIALS AND METHODS: By BCR-ABL mRNA quantification, we studied the serial pheresis products from 40 Philadelphia (Ph)-positive patients who received ICE/mini-ICE mobilization therapy and underwent autologous stem cell transplantation. We correlated the residual disease within the graft reinfused with the cytogenetic response following transplantation, taking into consideration those responses that lasted 12 months or more. RESULTS: Thirty-two patients received a graft with 0-35% Ph-metaphases and 19 received a graft with BCR-ABL/ABL ratio < or =0.01. After a median of 27 months (range, 12-50) from transplant, 18 patients achieved complete or major cytogenetic response lasting at least 12 months, and 14 of them (78%) received a graft with BCR-ABL/ABL ratio < or =0.01 (range, 0.0003-0.01). Twenty-two patients experienced short-lived responses or had >35% Ph-positive cells in the marrow after transplant, but only 5 of them (23%) had a graft with BCR-ABL/ABL ratio < or =0.01 (range, 0.001-0.01). Therefore, we found a strong association between a BCR-ABL/ABL ratio less than or =0.01 and the achievement of complete or major cytogenetic remission after autografting (chi(2) test, p = 0.0001). Patients reinfused with grafts contaminated at low levels with leukemic cells also showed a longer duration of the response (log-rank test, p = 0.0009). Eleven patients were reinfused with the lowest level of contaminated stem cell collections, according to the BCR-ABL/ABL ratio. None of these patients experienced prolonged neutropenia or thrombocytopenia following stem cell reinfusion and nine of them had long-lasting complete or major cytogenetic responses after transplant. CONCLUSION: This study demonstrates that the number of BCR-ABL positive cells present in a stem cell graft is an important predictive factor for the achievement and the duration of cytogenetic response after autografting. [corrected]

Adult↗
PubMed1998

The importance of cytogenetics and associated molecular techniques in the management of patients with leukaemia.

The cytogenetic analysis of haematological malignancies plays a major role in diagnosis. A large number of non-random chromosomal abnormalities are associated with specific types of leukaemia. Often, the cytogenetic result provides the definitive diagnosis. The recent developments in molecular cytogenetic technologies, in association with conventional cytogenetic analysis, have improved the accuracy of the results and led to the finding of new chromosomal abnormalities in leukaemia. Patients may be monitored by cytogenetics, molecular techniques and/or fluorescence in situ hybridization (FISH) during the course of their management, for evidence of minimal residual disease. These techniques also provide a useful method for monitoring patients following bone marrow transplantation, particularly when the patient and the donor are of the opposite sex. The cytogenetic result is an independent prognostic indicator, with certain karyotypes associated with a good prognosis, although others indicate a poor outcome.

Bone Marrow Transplantation↗
PubMed2004

Cytogenetic abnormalities in de novo acute myeloid leukemia in adults: relation to morphology, age, sex and ethnicity - a single center study from Singapore.

BACKGROUND: Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute myeloid leukemia (AML). Large systematic studies of cytogenetic abnormalities in AML patients from Southeast Asia are not available. The karyotypic patterns in AML patients from a single center in Singapore were studied and compared with reports from other regions of the world to identify possible geographic heterogeneity. METHODS: Analysis was performed on 501 consecutive de novo AML patients diagnosed according to the FAB criteria in the Singapore General Hospital. The cytogenetic findings were analyzed for possible associations between karyotypic pattern and the age, gender, ethnicity as well as morphological (FAB) subtypes. RESULTS: A total of 454 patients were studied of which 275(61%) had abnormal cytogenetics(median age 48 years). The t(15;17) and trisomy 8 were the most frequent karyotypic abnormalities - seen in 52(11%) and 33(7.3%) cases, respectively. Inv(lf) and t(16;16) were uncommon, seen only in five (1.1%) cases. The abnormalities del 5/5q and del 7/7q were seen in 30(6.6%) and 32(7%) of the cases. Complex karyotypes were seen in 78(17%) of the cases.Recurrent cytogenetic abnormalities correlated with the FAB subtypes. In all, 21 novel cytogenetic abnormalities were observed. CONCLUSIONS: Certain differences such as the age at presentation and frequency of recurrent balanced translocations were noted in comparison to previous reports. These point to the need for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.

Acute Disease↗
PubMed1998

BCR-ABL-positive progenitors in chronic myeloid leukaemia patients in complete cytogenetic remission after treatment with interferon-alpha.

To determine the source of residual disease detected in patients with chronic myeloid leukaemia (CML) in complete cytogenetic remission (n=8) after treatment with interferon-alpha (IFN-alpha), we have tested CFU-GM colonies grown from bone marrow mononuclear cells or from plastic-adherent (Pdelta) cells for BCR-ABL mRNA using a nested multiplex RT-PCR. We compared our results with those obtained by analysis of colonies from newly diagnosed patients (n=4) and patients achieving no cytogenetic response (n=1) or incomplete cytogenetic response to treatment with IFN-alpha (n=5). A total of 1239 informative colonies were analysed. A small proportion of BCR-ABL-positive colonies was detected in all eight patients in complete cytogenetic remission, suggesting the persistence of leukaemia that could potentially lead to relapse. The overall proportion of BCR-ABL-positive colonies in patients achieving a cytogenetic response to IFN-alpha correlated with the levels of BCR-ABL transcripts detected in the peripheral blood by competitive RT-PCR (P=0.004). We conclude that residual disease detected in the peripheral blood of complete cytogenetic responders to IFN-alpha is at least partly derived from clonogenic myeloid cells. It is probable that the leukaemia clone in CML is only very rarely or never entirely eradicated by treatment with IFN-alpha.

Adult↗
PubMed2002

The post-transplant cytogenetic response to interferon is a major determinant of survival after autologous stem cell transplantation for chronic myeloid leukaemia in chronic phase.

We have analysed the outcome of 581 autologous stem cell transplants (SCT) for chronic myeloid leukaemia (CML) in first chronic phase reported to the European Group for Blood and Marrow Transplantation between 1983 and 1998. Out off 207 patients evaluable for cytogenetics within 6 months of SCT, 36 patients (17%) were in complete cytogenetic remission (CCR), 34 (16%) in major remission (MCR), 74 (36%) in minor remission (mCR) and 63 (31%) had no cytogenetic response (NR). Interferon (IFN) was given post SCT to 267 patients. Results of the cytogenetic analysis within 1-2 years from SCT were available for 117 patients, the majority of whom (n = 101) received IFN post SCT: 17 (15%) were in CCR, 18 (15%) in MCR, 24 (20%) in mCR and 58 (50%) NR. The median survival in this series was 96 months (71-125) from SCT. There was no difference in survival according to cytogenetic status pre- and immediately post SCT. However, patients in CCR or MCR at 1-2 years post SCT had a 10-year survival of 66% compared with 36% for patients in mCR or NR (P = 0.003). The 5-year survival for patients receiving IFN post SCT was 72% compared with 61% for patients not treated with IFN (P = 0.01). Out of 155 patients refractory to IFN pre SCT, 70% achieved a cytogenetic response post SCT, which was complete or major in 31%. IFN refractory patients who sustained a CCR or MCR for 1-2 years after SCT had an excellent outcome.

Adult↗
PubMed1997

Prognostic implications of cytogenetic findings in kidney cancer.

OBJECTIVE: To evaluate the prognostic impact of cytogenetic findings in renal cell carcinoma (RCC). PATIENTS AND METHODS: Tumour cytogenetics, histomorphology, DNA ploidy and S-phase fraction, stage, size, and grade were related to survival in 50 consecutive patients with RCC. The mean follow-up was 3.9 years (median 4.2, range 0-8.8). RESULTS: The predictive probability for recurrence-free survival at 5 years (5-year RFS) for all 50 patients was 0.54. There was a significant association between the degree of cytogenetic complexity and survival, in that patients with five or less aberrations had a better prognosis than those with more than five changes (5-year RFS 0.71 and 0.43, respectively; P < 0.05). Patients with del(8p)/-8, +12, and +20 had a significantly worse prognosis compared with those without these aberrations. Of the well-known prognostic variables grade and stage, the former was far better for predicting prognosis. A Spearman correlation test showed a significant covariation of grade with the S-phase fraction, T-stage, and cytogenetic complexity. CONCLUSION: The degree of cytogenetic complexity and recurrent cytogenetic abnormalities affect the prognosis in RCC, although grade was the most reliable independent prognostic factor predicting disease recurrence.

Carcinoma, Renal Cell↗
PubMed2001

Molecular characterization of the deletion in retinoblastoma patients with 13q14 cytogenetic anomalies.

We investigated the molecular deletions of twelve patients presenting with retinoblastoma and a cytogenetic abnormality including band 13q14. Dinucleotide markers spanning the complete chromosome 13 as well as two intragenic markers were analyzed in patients and their two parents. The deletion was considered confirmed when one heterozygous allele was missing, potential when a homozygous allele was observed in continuity with a clearly deleted allele, and noninformative when a homozygous allele was observed adjacent to a nondeleted region. The patients could be classified into three groups based on their cytogenetic abnormalities. In group 1, the cytogenetic deletion was restricted to band13q14 with confirmed or potential molecular deletions extending from D13S328 to D13S153. Although a possible common centromeric deletion breakpoint could exist for three of the patients and a common telomeric deletion breakpoint for two, the cytogenetic deletion was different for most of them. Group 2 included patients with a cytogenetic deletion extending up to 13q22. At the molecular level, the telomeric breakpoints were between the RB1 gene and D13S156. Here again, it is quite unlikely that a common telomeric breakpoint was responsible for the deletion. Group 3 consisted of special cases with either a paracentric inversion or a complex translocation. The cytogenetic abnormalities around 13q14 correlate with the molecular deletions that were observed in this study. Associated malformations cannot be easily predicted from the size of the deletions.

Child, Preschool↗
PubMed1996

Comparison of fluorescence in situ hybridization, cytogenetic analysis, and DNA index analysis to detect chromosomes 4 and 10 aneuploidy in pediatric acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: Chromosome abnormalities are an important prognostic factor in childhood acute lymphoblastic leukemia (ALL). Recently, a subset of patients with hyperdiploid ALL and trisomy of chromosomes 4 and 10 has been reported to have a very favorable event-free survival. Rapid and accurate detection of these patients will allow them to be treated with highly effective and relatively nontoxic antimetabolite therapy. Because of inherent problems associated with conventional cancer cytogenetics, we examined the efficacy of fluorescence in situ hybridization (FISH) to identify this ALL subgroup. PATIENTS AND METHODS: Fifty uncultured bone marrow specimens from children with newly diagnosed ALL were examined for chromosomes 4 and 10 aneuploidy with FISH. These results were compared with routine cytogenetics and DNA Index (DI). RESULTS: Interphase FISH cytogenetics identified the abnormal cell line(s) in all cases in which cytogenetics showed aneuploidy of chromosomes 4 and 10. In cases in which cytogenetics was not informative, FISH identified the presence of an aneuploid chromosome 4 and/or 10 cell line in concordance with the DI. CONCLUSIONS: FISH interphase cytogenetics can accurately detect chromosome 4 and 10 aneuploidy in leukemic cells. It is a rapid and clinically applicable technique that can reliably identify childhood ALL cases who have trisomy of chromosomes 4 and 10 and who have very favorable event-free survival.

Aneuploidy↗
PubMedDate not supplied

Prenatal diagnosis from fetal urine in bladder outlet obstruction: success rates for traditional cytogenetic evaluation and interphase fluorescence in situ hybridization.

PURPOSE: To determine the optimal approach to the prenatal chromosome analysis of fetal urine from fetuses with bladder outlet obstruction. METHODS: Retrospective evaluation of traditional cytogenetic and interphase fluorescence in situ hybridization (FISH) analysis on fetal urine specimens from fetuses with bladder outlet obstruction. RESULTS: Traditional cytogenetic analysis was successful on 71 (95%) of 75 samples, and FISH was informative on 20 (65%) of 31 specimens. The combination of traditional cytogenetic analysis and FISH yielded a 96% diagnostic success rate. The mean turnaround time was 8 days (range 5-14) for traditional cytogenetic analysis and 1.6 days (range 1.0-4.0) for FISH. Chromosome abnormalities were detected in 6 (7.9%) of 76 pregnancies. CONCLUSION: Traditional cytogenetic analysis achieves a high success rate (95%) and is superior to FISH for chromosome evaluation of fetal urine. However, FISH, when informative, can complement traditional cytogenetics as it will expeditiously rule out common trisomies in fetuses with bladder outlet obstruction.

Female↗
PubMed2006

Various distinctive cytogenetic abnormalities in patients with acute myeloid leukaemia aged 60 years and older express adverse prognostic value: results from a prospective clinical trial.

Diagnostic cytogenetic abnormalities are considered important prognostic factors in patients with acute myeloid leukaemia (AML). However, the prognostic assessments have mainly been derived from patients with AML aged <60 years. Two recent studies of AML patients of 60 years and older proposed prognostic classifications with distinct discrepancies. To further study the prognostic value of cytogenetic abnormalities in this patient population, we have evaluated cytogenetic abnormalities in a series of 293 untreated patients with AML aged 60 years and older, included in a randomised phase 3 trial, also in relation to patient characteristics and clinical outcome. The most frequently observed cytogenetic abnormality was trisomy 8 (+8), in 31 (11%) patients. Abnormalities, such as -5, 5q-, abn(17p) and abn(17q), were almost exclusively present in complex karyotypes. A relatively favourable outcome was only observed in five patients with core-binding factor abnormalities t(8;21) and inv(16)/del(16)/t(16;16). However, most of the other evaluated cytogenetic abnormalities, such as 5q-, -7, +8, abn(17p), abn(17q), and complex aberrations expressed a more adverse prognosis when compared with patients with AML aged 60 years and older with a normal karyotype. Large studies to confirm the prognosis of individual cytogenetic aberrations are warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Prognostic impact of interferon alpha-induced cytogenetic remission in chronic myelogenous leukaemia: long-term follow-up.

To evaluate the long-term impact of the reduction of Philadelphia chromosome (Ph)-positive metaphases by treatment of chronic myelogenous leukaemia (CML) with interferon (IFN) alpha, we examined the outcome of 62 patients who had been enrolled between 1984 and 1990 into 2 IFN trials at our institution. As best cytogenetic response, 9 patients had achieved a complete remission and an additional 9 patients a partial remission. The remaining 44 patients had obtained either a minimal (n=29) or no cytogenetic response (n=15). Of the total of 62 patients, 9 were still on schedule and responsive to IFN in January 1995, including 7 patients in ongoing complete cytogenetic remission. The overall 5-year survival rate after a median follow-up from diagnosis of 51 months (range 3-102 months) was 62% and the median survival was reached at month 87. The effect of cytogenetic remission on survival was examined by "landmark" studies showing a significant survival advantage for patients with karyotype responses. In conclusion, in the patients studied, cytogenetic improvement was found to translate into improved survival expectancy. Long-term control by IFN alpha of CML, however, was restricted to a small minority of patients, predominantly to those attaining a complete suppression of the leukaemic cell clone as judged by cytogenetic criteria.

Actuarial Analysis↗
PubMed1995

Comparison of high resolution cytogenetics, fluorescence in situ hybridisation, and DNA studies to validate the diagnosis of Prader-Willi and Angelman's syndromes.

Eighty seven referrals with Prader-Willi syndrome and 49 with Angelman's syndrome were studied. High resolution cytogenetics was performed on all probands. Molecular studies, performed on the proband and both parents in each case, utilised multiple probes from within and distal to the 15(q11-13) region in order to establish the presence of DNA deletion or uniparental disomy. In addition, FISH, with probes at D15S11 and GABR beta 3 from the Prader-Willi syndrome/Angelman's syndrome region, was performed on a subset of 25 of these patients. In the referral group with Prader-Willi syndrome, 62 patients had a normal karyotype and 25 were deleted on high resolution cytogenetics. Twenty nine were found to be deleted with DNA techniques. In the Angelman's syndrome group, 37 had a normal karyotype and 12 were deleted on high resolution cytogenetics while 26 were deleted on molecular studies. The diagnosis was reassessed in 35 referrals with Prader-Willi syndrome and 11 with Angelman's syndrome following a non-deleted, non-disomic result. Of individuals who were neither deleted nor disomic on DNA studies, a false positive rate of 11.4% (4/35) for Prader-Willi syndrome and 16.7% (2/12) for Angelman's syndrome was found for a cytogenetically detected deletion. The false negative rate for deletion detected on high resolution cytogenetics was 19.5% (12/62) for Prader-Willi syndrome and 35% (13/37) for Angelman's syndrome. Thus high resolution cytogenetics was shown to be unreliable for deletion detection and should not be used alone to diagnose either syndrome. There were no discrepancies with FISH in 25 cases when FISH was compared with the DNA results, indicating that FISH can be used reliably for deletion detection in both syndromes.

Adolescent↗
PubMedDate not supplied

Acute cytogenetic effects of antineoplastic drugs on peripheral blood lymphocytes in cancer patients chromosome aberrations and micronuclei.

AIMS AND BACKGROUND: The aim of the present study was to evaluate the individual sensitivity of cancer patients to different antineoplastic drugs administered in standard protocols by assessing their acute cytogenetic effects on peripheral blood lymphocytes. METHODS AND STUDY DESIGN: In 12 patients undergoing cancer chemotherapy, acute cytogenetic effects on peripheral blood lymphocytes were evaluated by analysis of structural chromosome aberrations and micronuclei. All patients were given antineoplastic drugs, mainly as polychemotherapy. The frequencies of both cytogenetic biomarkers determined after the first chemotherapy cycle were compared with their pre-treatment (baseline) values. RESULTS: All chemotherapy protocols employed induced clear cytogenetic effects in both tests studied. The results obtained indicate interindividual variations between cytogenetic damage in peripheral blood lymphocytes among cancer patients. Statistically significant increases in the total number of structural chromosome aberrations and micronuclei in lymphocytes analyzed after chemotherapy compared to pre-therapy samples were observed in almost all patients studied. The highest level of chromosome damage as well as the highest incidence of micronuclei was observed following administration of the ACOP protocol (adriamycin, cyclophosphamide and vincristine). The proportions of signal-positive and signal-negative micronuclei were evaluated using DAPI staining, while silver staining revealed Ag-NOR+ and Ag-NOR- micronuclei. In some patients the incidence of signal-positive and Ag-NOR+ micronuclei after treatment was increased, indicating a more pronounced susceptibility of particular chromosomes to damage caused by antineoplastic drugs. CONCLUSIONS: With regard to the results obtained we may conclude that both parameters used in the present study on peripheral lymphocytes are sensitive biomarkers and can be successfully employed for biomonitoring of acute cytogenetic effects induced by antineoplastic drugs in standard clinical protocols for cancer treatment.

Adult↗