Valuation of Cytogenetics and FISH in Evaluation of Myelodysplastic Syndromes: A Cancer Cytogenetics Reference Lab’s Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1441-1441
Author(s):  
Guoxian Sun ◽  
Michael Lorenzo ◽  
Joseph Tripodi ◽  
Chrysostomos Chrysostomou ◽  
Christine F. Stephenson ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Cytogenetic Analysis ◽  
Cell Biology ◽  
Genetic Defect ◽  
Cost Effective ◽  
Chromosome Morphology ◽  
Chromosome 8 ◽  
Trisomy 8 ◽  
Additional Information ◽  
Panel Testing

Abstract Cytogenetics has proven an essential tool not only for confirming a diagnosis/classification, but for providing prognostic value as well in myelodysplastic syndromes (MDS). However, approximately 50% of primary MDS do not show discernible chromosome changes. In recent years, the fluorescence in situ hybridization (FISH) technique using gene or chromosome locus/region specific probes has emerged as a promising test in various hematopoietic and lymphoid neoplasms. To evaluate the application of FISH panels and cytogenetic studies in MDS, we retrospectively analyzed 1,885 consecutive bone marrow results from patients with suspected MDS due to cytopenia(s). In particular, we assessed the additional information a FISH reflex testing might have given in cytogenetically normal cases. The probes used in the panel included the EGR1 at 5q31, the D7S522 at 7q31, the D8Z2 for the centromere of chromosome 8, the MLL at 11q23 and the D20S108 at 20q12 (Vysis, Inc.). Among all patients, 190 (10%) had clonal chromosome abnormalities, mostly as reported in the literatures, eg, -5/5q- accounted for 34.7% of abnormalities, trisomy 8 29.5%, -7/7q- 14.2%, 20q- 13.7%. Of 345 cases with a FISH reflex test ordered and performed, only 3 (0.87%) showed positive results: a deletion of 7q31, a deletion of 20q12 and a deletion of 5q31 in 9.6%, 8.2% and 71.5% of interphase cells respectively. For the case with 5q- detected by FISH, only 12 metaphases were available for cytogenetic analysis. From our data and experience, at present, interphase FISH panel testing seems not to be an efficient and cost-effective method used as a screening test for cytopenia(s) in the diagnosis of MDS, different from its applications in B-cell chronic lymphoid leukemias, non-Hodgkin lymphomas and plasma cell neoplasms where neoplastic cells inherited not to divide easily in culture for metaphase analysis. Rather, it should be used for suspected MDS cases as a technique of choice for problematic specimens compromised for cytogenetic analysis such as cellular insufficiency, extended transit time and extremely low mitotic index or poor chromosome morphology. Until more genetic defect targeted probes become available with a better understanding of the stem cell biology and pathogenesis in MDS, cytogenetics is still the best and a “must” technique for detecting genomic aberrations in MDS and nearly all other myeloid hematopoietic neoplastic disorders.

scholarly journals Aberrations of chromosome 8 in myelodysplastic syndromes: Clinical and biological significance

2006 ◽  
Vol 134 (9-10) ◽  
pp. 404-407
Author(s):  
Dragomir Marisavljevic ◽  
Milena Pantic-Ludoski ◽  
Angelina Novak ◽  
Vesna Djordjevic
Keyword(s):  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
Direct Method ◽  
Genetic Material ◽  
Biological Significance ◽  
Chromosome 8 ◽  
Response To Treatment ◽  
Trisomy 8 ◽  
Single Chromosome ◽  
Normal Cytogenetics

Introduction: Rearrangements of any single chromosome in human karyotype have been reported in patients with pMDS. Objective: To examine the role of aberrations of chromosome 8 in pathogenesis, clinical presentation and progression of myelodysplastic syndromes. Method: Cytogenetic analysis of bone marrow cells was carried out by direct method and by means of 24- and/or 48-hour unstimulated cell culture. Chromosomes were obtained by modified method of HG-bands. Results: On presentation, 109 out of 271 successfully karyotyped patients (40,2%) had abnormal karyotypes. Among them, 22 patients (10.9%) had aberrations of chromosome 8. Ten patients had trisomy 8 as "simple" aberration whilst additional three cases had trisomy 8 included in "complex" karyotypes (?3 chromosomes). Cases with constitutional trisomy 8 mosaicism (CT8M) were excluded using the chromosome analyses of PHA-stimulated blood cultures. On the contrary, monosomy (seven patients) or deletion of chromosome 8 (two patients) were exclusively found in "complex" karyotypes. During prolonged cytogenetic follow-up, trisomy 8 was not recorded in evolving karyotypes. In contrast, trisomy 8 disappeared in two cases during subsequent cytogenetic studies, i.e. 23 and 72 months from diagnosis, accompanied in one patient with complete hematological remission. No difference regarding age, sex, cytopenia, blood and marrow blast count or response to treatment was found between patients with trisomy 8 as the sole aberration compared to those with normal cytogenetics. Median survival of patients with trisomy 8 as the sole aberration was 27 months, as compared to 32 months in patients with normal cytogenetics (p=0.468), whilst median survival of patients with aberrations of chromosome 8 included in "complex" karyotypes was only 4 months. Conclusion: Aberrations of chromosome 8 are common in patients with pMDS. The presence of a clone with trisomy 8 is not always the sign of disease progression or poor prognosis in MDS patients, in contrast to clones with aberrations of chromosome 8 manifesting the loss of genetic material.

scholarly journals Characterization of Cytogenetic Abnormalities in Myelofibrosis and Relationship to Clinical Outcome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1937-1937
Author(s):  
Andrew Kuykendall ◽  
Chetasi Talati ◽  
Najla H Al Ali ◽  
Eric Padron ◽  
David Sallman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Polycythemia Vera ◽  
Cytogenetic Analysis ◽  
Research Funding ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Chromosome 8 ◽  
Trisomy 8 ◽  
Cytogenetic Abnormalities ◽  
Trisomy 9

Abstract Introduction: Cytogenetic abnormalities occur frequently in patients with myelofibrosis (MF) and carry significant prognostic value. A variety of cytogenetic abnormalities have been reported with variable incidence. While the prognostic significance of more common cytogenetic abnormalities is well documented, the prognostic significance of less common abnormalities are difficult to discern due to limiting cohort size. Further, the specific phenotype associated with various cytogenetic abnormalities is less clear. We reviewed our institutional experience in an effort to describe the spectrum of chromosomal abnormalities, assess their correlation with clinical features, and validate their prognostic impact in a cohort of MF patients. Methods: This was a single institution, retrospective study of all patients with a diagnosis of MF who were seen at our center between 2/2001 - 6/2016.We reviewed cases of myelofibrosis in the Moffitt Cancer Center database. Definitions of primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (post-ET MF) and post-polycythemia vera myelofibrosis (post-PV MF) were according to World Health Organization 2016 criteria and the International Working Group for Myeloproliferative Neoplasms, Research and Treatment, respectively. Cytogenetic analysis was documented with preference to date of diagnosis. Overall survival was measured from time of cytogenetic analysis. Results: We identified 312 eligible. Cytogenetic data were available in 278 of 312 (89%) patients. The cohort was 59% male with a median age of 70 years at time of first presentation. PMF comprised 76% of cases with post-PV MF and post-ET MF accounting for 9% and 15% of cases respectively. Cytogenetic analysis was performed within 3 months of diagnosis in 63% and over a year after diagnosis in 24% of patients. Cytogenetic spectrum and frequency is shown in Figure 1. Normal diploid karyotype was present in 55%. The most common cytogenetic abnormality was a deletion of the long arm of chromosome 20 (del 20q), occurring in 39 (14%) cases. Del 20q occurred as an isolated abnormality in 26/39 cases. When occurring in conjunction with other structural abnormalities, it was most often associated with trisomy 9 (6/39). A deletion of the long arm of chromosome 13 (del 13q) was the second most common chromosomal aberration, occurring in 26 (9%) of cases and usually presenting as the sole abnormality (15/26). An extra copy of chromosome 8 (trisomy 8) occurred in 21 (8%) cases and often occurred in conjunction with other cytogenetic abnormalities (11/21). Less common cytogenetic abnormalities included trisomy 9, deletion 7q and deletion 5q, occurring in less than 4% of cases. Monosomal and complex karyotypes accounted for 10% and 8.3% of cytogenetics, respectively. We then assessed relationships between cytogenetic abnormalities and clinical and pathologic features. Del20q was associated with a lower IPSS score (r = -0.18, p = 0.0006). Deletion 13q was associated with older age at presentation (r = 0.14, p = 0.007). Prevalence of trisomy 8 was highest in post-polycythemia vera myelofibrosis (r = 0.14, p = 0.03) and associated with increased peripheral blast percentage (r = 0.16, p < 0.0001). Deletion 5q was associated with decreased hemoglobin (r = -0.13, p = 0.04), transfusion dependence (r = 0.20, p = 0.0009) and conversion to blast phase (r = 0.23, p = 0.0001). Patients with del 20q, del 13q, and trisomy 9 had median overall survival (OS) comparable to patients with a normal karyotype (45 vs 54 months, respectively, p = 0.69). Patients with unfavorable cytogenetic profiles (del 5q, trisomy 8, and chromosome 17 abnormalities) had significantly worse OS when compared to patients with normal diploid karyotype (20 vs 54 months, p = 0.0002) (figure 2). In multivariate regression analysis, controlling for DIPSS, deletion 5q (HR: 0.34 [0.15-0.78]; p = 0.01) and trisomy 8 (HR: 0.35 [0.17-0.73]; p = 0.005) were significantly associated with inferior overall survival. Conclusions: Cytogenetic abnormalities in myelofibrosis provide significant prognostic discrimination in patients with myelofibrosis. Our findings validate the prognostic value of cytogenetics and raise possible heretofore unrecognized clinical associations. Disclosures Lancet: Novartis: Consultancy; Biopath Holdings: Consultancy; Karyopharm: Consultancy; Boehringer-Ingelheim: Consultancy; Quantum First: Consultancy; ERYtech: Consultancy; Pfizer: Research Funding; Celgene: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Kalo Bios: Consultancy; Baxalta: Consultancy; Amgen: Consultancy. Sweet:Incyte Corporation: Research Funding; Pfizer: Speakers Bureau; Karyopharm: Honoraria, Research Funding; Ariad: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Komrokji:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Speakers Bureau.

scholarly journals Tritsomy 8 Acute Myeloid Leukemia Analysis Reveals New Insights of DNA Methylome with Identification of HHEX as Potential Diagnostic Marker

2015 ◽  
Vol 7 ◽  
pp. BIC.S19614 ◽  
Author(s):  
Marwa H. Saied ◽  
Jacek Marzec ◽  
Sabah Khalid ◽  
Paul Smith ◽  
Gael Molloy ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Diagnostic Marker ◽  
Cpg Island ◽  
Global Analysis ◽  
Extra Chromosome ◽  
Chromosome 8 ◽  
Trisomy 8 ◽  
Acute Myeloid

Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI ( P = 7.88 · 10–11identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML.

Partial trisomy 8 mosaicism due to a pseudoisodicentric chromosome 8

2011 ◽  
Vol 155 (7) ◽  
pp. 1740-1744 ◽  
Author(s):  
Eyby Leon ◽  
Seema M. Jamal ◽  
Ying S. Zou ◽  
Jeff M. Milunsky
Keyword(s):  
Partial Trisomy ◽  
Chromosome 8 ◽  
Trisomy 8

scholarly journals Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes

Blood ◽  
1986 ◽  
Vol 67 (6) ◽  
pp. 1765-1772 ◽  
Author(s):  
RH Jacobs ◽  
MA Cornbleet ◽  
JW Vardiman ◽  
RA Larson ◽  
MM Le Beau ◽  
...  
Keyword(s):  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Cells ◽  
Normal Karyotype ◽  
Refractory Anemia ◽  
Survival Times ◽  
Trisomy 8 ◽  
Leukemic Transformation ◽  
Abnormal Karyotype

Abstract Forty-nine patients with primary myelodysplastic syndromes (MDS) were subclassified according to French-American-British (FAB) Cooperative Group criteria. Eight patients had acquired idiopathic sideroblastic anemia (AISA), ten had chronic myelomonocytic leukemia (CMMoL), 14 had refractory anemia (RA), nine had refractory anemia with excess blasts (RAEB), and five had refractory anemia with excess blasts in transformation (RAEB-T); three patients could not be subclassified. The actuarial median survival for patients with AISA or with RA had not been reached at 60 months of follow-up. The median survival times for patients with CMMoL, RAEB, and RAEB-T were 25, 21, and 16 months, respectively. The percentages of patients with each subtype who developed ANLL were none in AISA, 20% in CMMoL, 7% in RA, 56% in RAEB, and 40% in RAEB-T. Patients with CMMoL had a poor prognosis independent of transformation to acute nonlymphocytic leukemia (ANLL), whereas patients with RAEB and RAEB-T had a high incidence of transformation and short survival times. Clonal chromosomal abnormalities were present in bone marrow cells from 19 patients at the time of diagnosis, and two others developed an abnormal karyotype at the time of leukemic transformation. The most frequent abnormalities, including initial and evolutionary changes, were trisomy 8 (9 patients), deletion of 5q (4 patients), and deletion of 20q (4 patients). The median survival times were 32 months for patients with an abnormal karyotype, and 48 months for those with a normal karyotype (P = 0.2). Specific chromosomal abnormalities were not associated with particular histologic subtypes; however, a high percentage of patients with RAEB and RAEB-T had an abnormal clone (89% and 80%, respectively). The percentages of patients with clonal abnormalities were 13% for AISA, 20% for CMMoL, and 29% for RA. The MDS transformed to ANLL in 42% of patients with an abnormal karyotype, compared to 10% of those with an initially normal karyotype (P less than .01). Among patients with RA, RAEB, and RAEB-T, the risk of leukemic transformation was confined to those with an abnormal karyotype (P less than .01). Thus, in the present study, morphology and karyotype combined were the best indicators of outcome in patients with MDS.

scholarly journals Effect of Risk and Protective Decision Aids on Flood Preparation in Vulnerable Communities

2018 ◽  
Vol 10 (3) ◽  
pp. 401-417 ◽  
Author(s):  
Gabrielle Wong-Parodi ◽  
Baruch Fischhoff ◽  
Benjamin Strauss
Keyword(s):  
Decision Aids ◽  
Cost Effective ◽  
Control Group ◽  
Perceptions Of Risk ◽  
Additional Information ◽  
Vulnerable Communities ◽  
Protective Actions ◽  
Negative Effect ◽  
The Impact ◽  
Positive Effect

Abstract Although the risks of flooding demand responses by communities and societies, there are also many cost-effective actions that individuals can take. The authors examine two potential determinants of such adoption: individual predisposition to act and the impact of decision aids that emphasize the risk, the actions, both, or neither (control). Respondents are a representative sample (N = 1201) of individuals in the areas most heavily affected by Superstorm Sandy in 2012. The authors find that, in the overall sample, seeing protective actions coupled with risk information or alone produced higher rates of individuals reporting that they intended to take action preparing for future storms, compared to a control group receiving no additional information. Moreover, that occurred despite the aids reducing their perceptions of risk. The authors find that individuals who reported having taken previous action are more responsive to decision aid messages with the exception of the combined message (risk and protective actions)—which had a positive effect on those who had not acted previously, but a negative effect on those who had. These results suggest that, in communities that already are aware of their flood risks, the critical need is for authoritative, comprehensible information regarding the most feasible and cost-effective protective actions that they can take. Providing such information requires analysis to determine which actions qualify and a design process that incorporates user feedback to ensure that recommendations are easily understood and credible.

Coexistance of Multiple Myeloma and Myelodysplastic Syndrome or Lymphoid Diseases At Diagnosis: Evidence for Two Clonal and Independent Chromose Abnormalities

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5063-5063
Author(s):  
Hossein Mossafa ◽  
Sabine Defasque ◽  
Christine Fourcade ◽  
JeanPierre Hurst ◽  
Bertrand Joly
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Critical Role ◽  
Chromosome 8 ◽  
Trisomy 8 ◽  
Hematopoietic Stem ◽  
Monosomy 7 ◽  
Trisomy 12

Abstract Abstract 5063 Introduction, We describe the simultaneous presentation of multiple myeloma (MM) and yeloproliferative disorders (MPD) or lymphoid diseases (LD) at diagnosis. Therapy-related myelodysplasia (tMDS) occurring during the course of MM is generally believed as a result from hematopoietic stem cell-toxic therapies, such as ionizing radiation and alkylating agent-based chemotherapies (melphalan, nitrosoureas).Patients and methods, We study a total of 342 patients (151 F, 191 M; median age 68.1 years; range 42 to 93 Years), diagnosed with MM based on the International Staging System. The basis for inclusion of patients in this study was with previous untreated MM ones. The study was performed in accordance with the declaration of Helsinki. To determine whether chemotherapies for MM factors play the critical role in the development of secondary disease, simultaneously two different cultures were processed, an unstimulated 96 hours culture (U96HC) on whole BM(WBM), a short-time 24 hours culture (ST24HC) after CD138+ plasma cells (PCs) depleted on negative fraction (CD138- cells) of BM and the FISH was investigated on purified CD138+.All samples were enriched in PCs by the Automated Magnetic Cell Sorter (Miltenyi technology)proceeded with anti-CD138 specific antibodies applied. The CD138+ PCs and the CD138- cells were collected in different tubes. The CD138− cells were used for a ST24HC. FISH was performed on the purified CD138+, PCs with a recommended FISH panel (MM International Working Group). Screening was performed systematically for the following unbalanced alterations and reciprocal rearrangements: del(13)(q14)(D13S25), del(17)(p13)(TP53),+3(D3Z), +9(D9Z1), +15(D15Z14), t(4;14)(p16;q32)/IGH-FGFR3, t(11;14)(q13;q32)/IGH-CCND1 (Abbott).After observing the results of U96HC on whole BM (CD138+ and CD138− cells), ST24HC (CD138− cells) and FISH for each patient, two clone cytogenetically were distinct and unrelated chromosomal abnormalities were found in 40 (11.7%) of the 342 MM patients (6 F, 34 M; median age 74 years; range 42 to 87 Years) 34 had a MPD and 6 had a LD. A second immunophenotyping analysis confirmed the presence of those LD/MM simultaneous haematological malignancy. In the cases of the patients with MM/ MPD, the frequency of cytogenetic abnormality unrelated to the myeloma clone was respectively; the 20q deletion, detected for 13 the 34 patients, the 20q- is a sole abnormality for 12 cases and associated with a complex caryotype in 1 case. The trisomy of chromosome +8 was observed in 7 cases, the del(7q) or monosomy 7 in 5 cases, loss of gonosome Y in 4 cases, del(11) for 2 cases, translocation t(9;22) in one case, 5q abnormality in one case and trisomy 9 with JAK2 V617F mutation in one case. For the patients with MM/LD, 5 patients had a trisomy +12 and or trisomy +18 like sole abnormality or associated with others cytogenetics abnormalities and one patient had 6q deletion. Discussion, Whereas in the literature the most common cytogenetic abnormalities typifying MPD after alkylator-based therapy include partial or complete deletions of chromosomes 5, 7, and 20 as well as trisomy 8. In our study we observed those abnormalities with the same frequency for the patients had simultaneous MPD associated in untreated MM at diagnosis. Six patients had simultaneous LD and MM. The marginal zone lymphoma was confirmed for 3 patients. The CC observed a trisomy +12 for those three patients associated with +18 and +19 for 2 cases and del(13) and trisomy 3 for one among them. We demonstrated in untreated MM patients the coexistence of MM and MPD or LD at diagnosis with MPD-type or LD-type chromosome abnormalities within MM signature karyotype. We hence recommend that CC studies, 96 hours WBM, 24 hours on negative fraction CD138− cells and FISH on purified CD138+ PCs, the three should be an integral part of the evaluation of patients with MM at diagnosis into clinical trials using HDT is warranted to determine whether patients who are predisposed to developing tMDS/sAML, they can be identified prospectively. Disclosures: No relevant conflicts of interest to declare.

Array CGH As a Complementary Tool in the Diagnosis of Myelodysplastic Syndromes

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3827-3827
Author(s):  
María Abáigar ◽  
Eva Lumbreras ◽  
Irene Rodríguez ◽  
Javier Sánchez-del-Real ◽  
María Díez-Campelo ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Myelodysplastic Syndromes ◽  
Copy Number ◽  
Normal Karyotype ◽  
Chromosome 8 ◽  
Comparative Genomic ◽  
Whole Genome ◽  
Acgh Analysis ◽  
Conventional Cytogenetics ◽  
Copy Number Changes

Abstract Abstract 3827 Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological disorders in which diagnosis, risk stratification, and treatment selection are based on morphological and cytogenetic studies in bone marrow (BM) samples. MDS are characterized by several recurrent chromosomal abnormalities, most of them unbalanced, with a widely variable prognosis. The assessment of these genomic defects is essential for a correct risk stratification of these patients. However, conventional cytogenetic (CC) techniques are not sufficient for the study of all MDS patients, because of the high proportion of normal karyotypes (40–50%) and unsuccessful cytogenetics (10%) (defined as the absence of mitosis). Array-based comparative genomic hybridization (aCGH) technology allows the screening of copy number changes among the whole genome in one single experiment and offers a higher resolution than conventional cytogenetics. Aims: To assess the potential application of aCGH in the clinical diagnosis of MDS as complementary tool to conventional cytogenetics. Patients and Methods: The study cohort comprises a total of 263 patients: MDS (203) and MDS/MPN (60) patients that have been previously studied by CC and FISH. Among the whole series, 33 (12.5%) patients had no successful cytogenetic results due to the absence of mitosis. In the remaining 230 patients with evaluable metaphases, 42 (16%) had an aberrant, while 188 (71.5%) presented a normal karyotype. Within this last group, 141 had ≥20 good-quality metaphases evaluated, 37 had 10–20 metaphases studied, and 10 patients had ≤10 successful metaphases. Copy number changes were analysed in all patients included in the study using NimbleGen Human CGH 12×135K Whole-Genome Tiling Array (Roche NimbleGen). Sex-matched human commercial DNA samples were used as reference. Data were analysed using the segMNT algorithm in NimbleScanv2.6 Software. Subsequently all genomic abnormalities found by aCGH analysis were confirmed by FISH. Results: Using aCGH methodology, copy number changes (greater than 600 bp) were detected in 54 patients of the global series: 4.3% of the normal karyotype patients, 88.1% of cases with abnormal cytogenetics, and 27.3% of patients with unsuccessful cytogenetics. Overall a high correlation (94.3%) between the cytogenetic changes observed by CC and CGH arrays was observed. Thus aCGH analysis revealed the same genomic abnormalities showed by CC in 88.1% of patients. In the remaining 11.9% genomic results were discordant between aCGH and CC, because of the presence of balanced translocations, not assessable by aCGH, and clonal cell populations below 30%. Furthermore, additional genomic abnormalities (n=36) not detected by CC were found by aCGH. The most frequent aberrations were losses affecting chromosomes 5 (33%), 7/7q (17%), 20q (14%), and Y (14%), as well as gains involving chromosome 8 (14%). Interestingly, other abnormalities, mainly losses, were found in chromosomes 4, 12, and 17. Focusing on the 188 patients with normal karyotype by CC, the aCGH profiling results were concordant with cytogenetics in 98% of those patients with ≥20 metaphases studied and in 92% of those with 10–20 metaphases. However, only 80% of those patients with ≤10 successful metaphases and no changes by CC displayed no copy number changes by aCGH. The most frequent abnormality found by aCGH among these normal karyotype cases was the presence of 5q deletion (2%), while other chromosomes affected were 7, 8, 11, 12 and 20. All these abnormalities were confirmed by FISH. Regarding the patients with unsuccessful cytogenetics, 72.7% of cases displayed a normal aCGH profile, while 27.3% showed at least one genomic imbalance The most frequent genomic aberrations were losses in 4q (6%), 5q (12%) and 7q (9%), and gain of chromosome 8 (6%). In addition, three of these cases showed a complex karyotype, showing more than 5 abnormalities. Conclusion: The use of aCGH karyotyping in the diagnosis of MDS could be used as a complementary technique to conventional karyotyping in the evaluation of MDS patients. Mainly in patients with unsuccessful cytogenetics and those with normal karyotype and <20 good-quality metaphases evaluated. Disclosures: Hernández: Celgene: Research Funding.

Cytogenetic Analysis in Patients with Newly Diagnosed Myelodysplastic Syndromes in Southern Italy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 50623-50623
Author(s):  
Esther Natalie Oliva ◽  
Francesco Albano ◽  
Nicola Di Renzo ◽  
Vincenzo Pavone ◽  
Stefano Molica ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Cytogenetic Analysis ◽  
Southern Italy ◽  
Conflicts Of Interest ◽  
Refractory Anemia ◽  
Newly Diagnosed ◽  
Conventional Cytogenetic Analysis ◽  
Conventional Analysis ◽  
Italian Regions

Abstract Abstract 50623 Background: Bone marrow karyotype in myelodysplastic syndromes (MDS) is essential to define the prognosis and to guide treatment decisions, including targeted therapies. Due to the lack of an extensive national MDS registry in Italy, epidemiological data on MDS, including cytogenetics, throughout the territory is unknown. Objective: We evaluated the incidence of cytogenetic abnormalities amongst newly diagnosed MDS patients in in 2 southern Italian regions (Calabria and Puglia). Methods: A pilot project, denominated ANDROMEDA (ANalysis of cytOgenetics alteRatiOn in the MyEloDysplAstic syndromes) was developed in 17 centers to offer a service of conventional cytogenetic analysis for all consecutive patients undergoing diagnostic evaluation for cytopenia and suspected MDS between January 1 and December 31, 2011. The study conformed to the ethical standards set out in the Declaration of Helsinki and was approved by institutional review boards at each participating center. Patients were required to provide their written informed consent. Clinical characteristics of patients and bone marrow morphology, iron staining and histology were registered. Bone marrow samples were centralized for standard cytogenetic studies and fluorescence in situ hybridization to two dedicated genetics laboratories (one for each region), blind to patients' data. Results: Two hundred and thirty-five patients were evaluated and MDS diagnosis was confirmed in 220 cases (88. 3%), according to WHO criteria. The overall incidence of clonal chromosome abnormalities detected by conventional analysis was 36. 9%. Single abnormalities included +8 (13 cases, 5. 8%), del(5q) (12 cases, 5. 4%), –Y (11 cases, 5. 0%) and del(7)/-7 (4 cases, 1. 8%). Complex karyotypes were detected in 18 (8. 1%) cases. Among all cases only 10 (4. 5%) bone marrow samples were not evaluable for cytogenetic analysis. FISH revealed additional abnormalities not identified by conventional analysis only in 3 (1. 3%) out of 72 cases. Patients were classified in WHO subtypes: 39. 2% refractory cytopenia with unilineage dysplasia (RCUD), 1. 5% refractory anemia with ring sideroblasts (RARS), 32. 5% refractory cytopenia with multilineage (RCMD), 10. 8% refractory anemia with excess of blast-1 (RAEB-1), 9. 3% refractory anemia with excess of blast-2 (RAEB-2), 4. 1% MDS with deletion 5q (MDS 5q-) and 2. 6% MDS unclassifiable (MDS-U). Conclusions: These preliminary results demonstrate that the incidence of abnormal karyotype patterns and WHO subgroups in MDS patients in Southern Italy is comparable with that described in other geographical areas. It is confirmed that conventional cytogenetic analysis is a standard in the diagnostic workup of MDS of patients with a suspected myeloid malignancy in order to identify primary abnormalities and prognostic models. Disclosures: No relevant conflicts of interest to declare.

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