scholarly journals Analyzing The Mutations Of Notch1 And Sf3b1 Genes In Cases With CLL Detected Isolated 13q Deletion

2021 ◽  
Author(s):  
Gülçin GÜNDEN ◽  
Sevgi IŞIK ◽  
Hava ÜSKÜDAR TEKE ◽  
Oğuz ÇİLİNGİR ◽  
Nur OGUZ DAVUTOGLU ◽  
...  
Keyword(s):  
13Q Deletion

scholarly journals Chromosome 13q deletion syndrome involving 13q31-qter: A case report

2017 ◽  
Vol 15 (6) ◽  
pp. 3658-3664 ◽  
Author(s):  
Yue-Ping Wang ◽  
Da-Jia Wang ◽  
Zhi-Bin Niu ◽  
Wan-Ting Cui
Keyword(s):  
Case Report ◽  
Deletion Syndrome ◽  
Chromosome 13Q ◽  
13Q Deletion

scholarly journals Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4696-4700 ◽  
Author(s):  
Nikhil C. Munshi ◽  
Kenneth C. Anderson ◽  
P. Leif Bergsagel ◽  
John Shaughnessy ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
High Risk ◽  
Risk Stratification ◽  
Fluorescence In Situ Hybridization ◽  
High Serum ◽  
Β2 Microglobulin ◽  
Poor Outcome ◽  
13Q Deletion

Abstract A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β2-microglobulin level and International Staging System stages II and III, incorporating high β2-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.

Retinoblastoma and the 13q Deletion Syndrome

2001 ◽  
Vol 38 (4) ◽  
pp. 247-250
Author(s):  
Anuradha Ganesh ◽  
Ravinder K Kenue ◽  
Sandip Mitra
Keyword(s):  
Deletion Syndrome ◽  
13Q Deletion

Molecular Classification of Multiple Myeloma: A Distinct Transcriptional Profile Characterizes Patients Expressing CCND1 and Negative for 14q32 Translocations

2005 ◽  
Vol 23 (29) ◽  
pp. 7296-7306 ◽  
Author(s):  
Luca Agnelli ◽  
Silvio Bicciato ◽  
Michela Mattioli ◽  
Sonia Fabris ◽  
Daniela Intini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Pattern ◽  
Marker Genes ◽  
Published Data ◽  
Cyclin D ◽  
Chromosome 13Q ◽  
13Q Deletion

Purpose The deregulation of CCND1, CCND2 and CCND3 genes represents a common event in multiple myeloma (MM). A recently proposed classification grouped MM patients into five classes on the basis of their cyclin D expression profiles and the presence of the main translocations involving the immunoglobulin heavy chain locus (IGH) at 14q32. In this study, we provide a molecular characterization of the identified translocations/cyclins (TC) groups. Materials and Methods The gene expression profiles of purified plasma cells from 50 MM cases were used to stratify the samples into the five TC classes and identify their transcriptional fingerprints. The cyclin D expression data were validated by means of real-time quantitative polymerase chain reaction analysis; fluorescence in situ hybridization was used to investigate the cyclin D loci arrangements, and to detect the main IGH translocations and the chromosome 13q deletion. Results Class-prediction analysis identified 112 probe sets as characterizing the TC1, TC2, TC4 and TC5 groups, whereas the TC3 samples showed heterogeneous phenotypes and no marker genes. The TC2 group, which showed extra copies of the CCND1 locus and no IGH translocations or the chromosome 13q deletion, was characterized by the overexpression of genes involved in protein biosynthesis at the translational level. A meta-analysis of published data sets validated the identified gene expression signatures. Conclusion Our data contribute to the understanding of the molecular and biologic features of distinct MM subtypes. The identification of a distinctive gene expression pattern in TC2 patients may improve risk stratification and indicate novel therapeutic targets.

scholarly journals Comment to "Favorable outcome of patients who have 13q deletion: a suggestion for revision of the WHO 'MDS-U' designation" Haematologica. 2012;97(12):1845-9.

Haematologica ◽  
2013 ◽  
Vol 98 (4) ◽  
pp. e46-e47 ◽  
Author(s):  
A. Holbro ◽  
M. Jotterand ◽  
J. R. Passweg ◽  
A. Buser ◽  
A. Tichelli ◽  
...  
Keyword(s):  
Favorable Outcome ◽  
13Q Deletion

High Incidence of Translocations in CLL: A New Prognostic Marker for Infavorable Survival Outcome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 17-17 ◽  
Author(s):  
Christine Mayr ◽  
David M. Kofler ◽  
Raymund Buhmann ◽  
John Strehl ◽  
Raymonde Busch ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Chromosomal Aberrations ◽  
Cell Cycle Progression ◽  
Cd40 Ligand ◽  
Fish Analysis ◽  
Chromosome 11 ◽  
Cd38 Expression ◽  
High Incidence ◽  
13Q Deletion

Abstract BACKGROUND: Conventional metaphase cytogenetics underestimates the frequency of specific chromosome aberrations in B-CLL due to the low in vitro proliferative activity of CLL cells. We could recently show that stimulation of CLL cells with CD40 ligand (CD40L) induced cell cycle progression and increased the frequency of metaphases of CLL cells, which are then suitable for chromosome banding. In the present study we compared this new technique, CD40L-enhanced cytogenetics (CEC) with molecularcytogenetic data obtained by fluorescence in situ hybridization (FISH) on CLL cells. Methods: Blood samples were obtained from 95 CLL patients (Binet A: 31%, Binet B: 30%, Binet C: 39%) and subjected to simultaneous analysis by CEC and FISH. 56% of patients were previously untreated, while 44% of patients received at least one course of chemotherapy prior to the study. RESULTS: By FISH, 80% of analysed samples revealed aberrations like deletion of chromosome 11, 13 or 17 or trisomy 12. By CEC, chromosomal aberrations (range 0 to 14; median: 1) were detected in 90% of samples involving all chromosomes except the X chromosome. Importantly, a high incidence of balanced and unbalanced translocations were seen in 33 patients (35%) while 70% of the breakpoints involved were recurring. Median treatment-free survival (TFS) was significantly shorter for patients with translocations P< .0001). For patients with unbalanced translocations, overall survival was also significantly (decreased P= .0007). 25% of patients with 13q deletion as single aberration in FISH analysis additionally showed translocations (by CEC. These patients had a significantly shorter TFS compared to patients with 13q deletion as true sole aberration (median TFS: 36 mo vs. 132 mo; P= .0004). This was also true for patients with deletion of 11q. Patients with 11q- and translocations had a significant shorter TFS than patients with 11q- without translocations (median TFS: 13 mo vs. 48 mo; P= .011). All patients with 17p deletion showed translocations. In order to exclude the possibility that cytogenetic aberrations occurred as a possible treatment-associated secondary event, in a second analysis only patients who were untreated at the time of cytogenetic analysis were evaluated. In 22% of untreated patients translocations were detected and again they showed significantly lower TFS rates compared to patients without translocations (median TFS: 26 mo vs. 109 mo; P = .0128). In a multivariate analysis including Binet stage, presence of a complex karyotype (≥ 3 chromosomal aberrations), CD38 expression, 11q- and 17p-, the occurance of translocations proved to be the prognostic marker with the highest impact for an infavorable clinical outcome P< .001). CONCLUSION: Taken together, CEC is able to detect new chromosomal aberrations in CLL and enables a risk assessment for CLL patients based on the incidence of translocations otherwise indetectable by FISH or conventional metaphase cytogenetics.

PTEN Gene Deletions in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4889-4889
Author(s):  
Xiao Ying Qi ◽  
A. Keith Stewart ◽  
Hong Chang
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Myeloma Cell ◽  
Suppressor Gene ◽  
High Dose Chemotherapy ◽  
Pten Gene ◽  
Allelic Loss ◽  
High Dose ◽  
13Q Deletion

Abstract PTEN, a tumor suppressor gene, negatively regulates the anti-apoptotic action of akt phosphorylation. Allelic loss or mutation of this gene has been detected in many solid tumors and more recently in human myeloma cell lines (HMCLs). Expression of PTEN has resulted in growth inhibition and apoptosis of a HMCL, suggesting that it may play a role in the pathogenesis of multiple myeloma (MM). However, the PTEN status in tumor cells from patients with MM has not been determined. Using a triple staining method combining staining for cytoplasmic light chains and fluorescence in situ hybridization (FISH) with chromosome 10-centromere and PTEN-gene specific probes, we analyzed clonal plasma cells from 71 patients with MM, 10 with plasma cell leukemia (PCL) and 10 HMCLs. Hemizygous PTEN deletions were detected in 4 of 71 (5.6%) MM patients, 2 of 10 (20%) PCLs, and 2 of 10 (20%) HMCLs. The percentages of clonal plasma cells containing PTEN deletions ranged from 21–90% (median, 56%). Three of the 4 patients with PTEN deletions were detected at diagnosis with stage III disease (Duire-Salmon) and 1 was detected at relapse. Two patients had IgG kappa, 1 IgG lambda and 1 free lambda light chain. To correlate the PTEN status with other known genetic abnormalities in MM, we investigated 4 MM and 2 PCLs with PTEN deletions using FISH for chromosome13q, p53 status, translocations t(11;14), t(4;14) and t(14;16). One MM had a 13q deletion, 1 PCL had a t(11;14), and the other PCL had a t(14;16), a 13q deletion and a p53 deletion. All 4 MM patients with hemizygous PTEN deletions received melphalan based high-dose chemotherapy and autologous stem cell support. Their median overall survival (OS) was 48.1months, and progression free survival (PFS) was 42.8 months as compared to patients without PTEN deletions (OS, not reached, PFS, 25.8 months) (p=0.51 for OS, p=0.67 for PFS). Our results indicate that PTEN deletions are uncommon in MM patients and therefore unlikely represent a primary event for MM. PTEN deletions appear to occur in the advance stage of the disease, and are more frequently involved in PCL or HMCLs suggesting that deletions of PTEN may be associated with disease progression in a subset of MM.

Comparison of a Quantitative PCR Method with FISH for the Assessment of the Four Aneuploïdies Commonly Evaluated in CLL Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4950-4950
Author(s):  
Christian Bastard ◽  
Christophe Fruchart ◽  
Gregory Raux ◽  
Francoise Parmentier ◽  
Dominique Vaur ◽  
...  
Keyword(s):  
Quantitative Pcr ◽  
Target Genes ◽  
In Situ Hybridisation ◽  
Low Frequency ◽  
Proliferation Index ◽  
Trisomy 12 ◽  
Binet Stage ◽  
Pcr Method ◽  
Conventional Cytogenetics ◽  
13Q Deletion

Abstract Four chromosomal defects associated with prognosis have been identified in CLL patients, namely deletions of the 13q13-q14, 11q22 and 17p13 regions and trisomy 12. Due to the low proliferation index of these tumors and to the fact that some defects can be cryptic, the detection of these abnormalities by conventional cytogenetics is difficult. Therefore, the resulting aneuploidies are usually evaluated by fluorescent in situ hybridisation (FISH). As probes are expensive and FISH time consuming, we aimed to compare a quantitative PCR method - quantitative PCR of short fluorescent fragments (QMPSF) - with FISH for the detection of these acquired aneuploidies in a series of 110 patients with Binet stage A CLL. Genes located in the deleted or gained regions were selected as target genes - DLEU2 at 13q14, ATM at 11q22, p53 at 17p13, POU6F1 and MDM2 at 12q13 and 12q15 respectively - and amplified using a method based on the simultaneous amplification of short fluorescent genomic fragments under quantitative conditions. A chromosomal imbalance involving one or several of the four loci was detected in 76 patients (69%) either by FISH or QMPSF or both. A deletion of chromosome 13 was found in 61 patients (55%). A 11q22 deletion was present in 9 patients (8%), a trisomy 12 in 9 (8%) and a 17p deletion in one. The rather low frequency of the three latter defects reflects the fact that only patients with stage A CLL at diagnosis were studied, and neither stage B or C CLL. The 13q deletion was isolated in 53 patients and associated with a second defect in 8: these were six of the 11q22 deletions, one trisomy 12 and the 17p deletion. When the 13q deletion was associated with either a 11q deletion or a trisomy 12 both abnormalities were present in the same proportion of cells. This was not the case for the 17p deletion which appeared to be a secondary event, since, as evaluated by FISH, it was present in 24% of cells whereas the 13q deletion was present in 85% of interphase nuclei. FISH and QMPSF results were identical for 103 of 110 patients. The secondary 17p deletion was not detected whereas all other discrepancies could be explained. This study demonstrates that a single multiplex PCR can replace FISH in CLL patients. However, whereas QMPSF is perfectly adapted to the detection of primary defects, care should be taken when searching for minor clonal evolutions present in a small proportion of tumor cells.

Clinical Outcome of B-Cell Chronic Lymphocytic Leukemia Following Alemtuzumab Therapy: Retrospective Study within Various Cytogenetic Risk Categories

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3164-3164
Author(s):  
Michael Fiegl ◽  
Martin Erdel ◽  
Inge Tinhofer ◽  
Georg Hopfinger ◽  
Karin Eigenberger ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Cox Regression Analysis ◽  
Trisomy 12 ◽  
11Q Deletion ◽  
Cell Chronic Lymphocytic Leukemia ◽  
13Q Deletion

Abstract B-cell chronic lymphocytic leukemia (CLL) with 17p deletion responds poorly to chemotherapeutic agents. This retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced CLL, categorized by cytogenetic profile. Methods: This is the largest data base with efficacy analysis of alemtuzumab in CLL stratified according to cytogenetics. Detailed data analysis was done in 138 CLL patients, in whom cytogenetic analysis was performed by FISH using the standard CLL analysis categorized according to Doehner et al. (N Engl J Med343, 1910; 2000). Responses were evaluated according to the NCI criteria; progression-free survival (PFS) and overall survival (OS) were also assessed. Results: 73% of the patients were male. At start of alemtuzumab therapy, the median age was 64 years (range, 46–92); 12% were in Rai stage I, 18% in stage II, 20% in stage III, and 50% in stage IV. The median number of two prior therapies was 2 (range, 0–10); of the patients who received prior fludarabine (F) (n=113), 70% were F-refratory, 25% sensitive, and in 5% this was unknown. 30% and 17% of patients had bulky lymphadenopathy (&gt;5 cm) and giant splenomegaly (&gt;20 cm), respectively. Cytogenetic abnormalities were as follows: 13q deletion 14%; trisomy 12, 12%, 11q deletion 20%; 17p deletion, 33%, none of these, 22%. The overall response rate (ORR) was 38% in the total cohort. ORR was 53%, 56%, 21%, and 44% in the subgroup of 13q deletion, trisomy 12, 11q deletion, and 17p deletion, respectively; patients without any of these abnormalities had an ORR of 27%. From start of alemtuzumab, median PFS and OS for the whole cohort was 6.9 months and 30 months, respectively. Notably, PFS and OS in 17p deletion patients was 7.1 months and 19.1 months, respectively, an encouraging outcome when considering the unfavourable risk profile in these patients. In 17p deletion patients, response was remarkable also in disease involved lymph nodes (78%). Patients with F-resistant disease and 17p deletion, an extraordinarily poor prognostic group (n=25), had encouraging ORR, PFS, and OS rates (28%; 7.2 months; and 19.1 months, respectively), which did not differ from those in F-resistant patients with good risk cytogenetics. In a multivariate Cox regression analysis, independent risk factors for shorter OS were anemia (hazard ratio [HR] = 2.48; 95% CI, 1.50–4.11; P &lt;.001), ≥3 of prior lines of therapy (HR = 2.00; 95% CI, 1.24–3.24, P =.005), and poor risk cytogenetics ([17p deletion and 11q deletion], HR = 2.23; 95% CI 1.35–3.69, P =.002). Conclusion: Alemtuzumab was effective in CLL across all cytogenetic categories evaluated. In patients with favorable cytogenetics, we observed that alemtuzumab is a highly effective therapy even when conventional chemotherapy has failed. Patients with 17p deletion achieved quite favorable ORR and OS upon alemtuzumab. Thus, the 17p deletion group can often be shifted to an “intermediate” risk CLL, and responding patients are frequently re-treated with alemtuzumab.

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