Mosaic ring chromosome 8: Clinical and array-CGH findings in partial trisomy 8

2008 ◽  
Vol 146A (21) ◽  
pp. 2837-2841 ◽  
Author(s):  
Isabel Filges ◽  
Benno Röthlisberger ◽  
Friedel Wenzel ◽  
Karl Heinimann ◽  
Andreas R. Huber ◽  
...  
Keyword(s):  
Array Cgh ◽  
Ring Chromosome ◽  
Partial Trisomy ◽  
Chromosome 8 ◽  
Trisomy 8

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

Gene Amplifications In 84 Patients With Acute Myeloid Leukemia and 31 Patients With Myelodysplastic Syndrome Investigated By Array CGH

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3724-3724
Author(s):  
Andreas Roller ◽  
Simone Weber ◽  
Alexander Kohlmann ◽  
Melanie Zenger ◽  
Marita Staller ◽  
...  
Keyword(s):  
Array Cgh ◽  
Chromosomal Abnormalities ◽  
Ring Chromosome ◽  
Normal Karyotype ◽  
Structural Type ◽  
Single Copy ◽  
Chromosome 8 ◽  
Complex Karyotype ◽  
Employment Equity ◽  
Equity Ownership

Abstract Background Gains and losses of chromosomal material are frequent in AML and MDS and usually lead to loss or gain of a single copy of a whole chromosome, a chromosome arm or small stretches of the chromosome that may be microscopically invisible. More rarely, amplifications of chromosomal regions (defined as the presence of more than 6 copies of a region per cell) are observed. These supernumerary copies are located either extrachromosomally as small acentric chromosomal structures - so called double-minutes (dmin) - or intrachromosomally as large contiguous stretches of amplified DNA, so called homogeneously staining regions (HSR). Aims Characterize AML and MDS cases with gene amplifications with respect to size, affected genes and accompanying chromosomal abnormalities as well as TP53 status. Patients and Methods 84 AML and 31 MDS cases with cytogenetically visible amplifications were selected for this study. All cases were analyzed by array CGH, chromosome banding analysis, sequencing for TP53 mutations as well as FISH for TP53 deletions. Results The cohort comprised 55 (47.8%) males and 60 (52.2%) females with a median age of 72.0 years (range 38.0 - 90.3 years). A complex karyotype (≥4 aberrations) was present in 92/115 (80.0%) cases (AML=65/84 (77.4%); MDS=27/31 (87.1%)). In total, 385 amplified regions were identified by array CGH. In more detail: 3q26 (AML: n=6; MDS: n=3), 8q24 (AML: n=15; MDS: n=1), 11q21-25 (AML: n=42; MDS: n=13), 13q12 (AML: n=3; MDS: n=1), 13q31 (AML: n=3; MDS: n=2), 19p13 (AML: n=2; MDS: n=4), and 21q21-q22 (AML: n=24; MDS: n=5). The median number of amplified regions was 3 (range 1-18). In 14/115 (12.2%) cases, the amplification was located in dmins (AML: n=11; MDS: n=3) and in 101/115 (87.8%) patients in HSR (AML: n=73; MDS: n=28). In 40 of the latter 101 cases (39.6%) (AML: n=24; MDS: n=16) the amplification was located on a ring chromosome (rc). In patients with complex karyotypes we detected a significantly higher number of amplified regions as compared to non-complex karyotypes (3.5 vs. 2.8; p=0.015). No association between the complexity of the karyotype and the structural type of the amplification (dmin vs rc) was observed. Cases with non-complex karyotypes frequently harbored a 5q deletion (6/23; 26.1%) or chromosome 8 abnormalities (3/23; 13.0%). Within the subgroup of non-complex karyotypes del(5q) cases showed a tendency to a higher number of amplified regions (3.6 vs. 1.9; p=0.140). Further, amplifications of 11q genes were more frequent in complex karyotypes (54.4% vs. 21.7%; p=0.005), whereas 8q amplifications were more frequent in non-complex karyotypes (43.5% vs. 4.4%; p<0.001). We detected a large region on band 11q24, which was amplified in 41/53 (77.4%) cases. This commonly amplified region contains 1,575 genes including the MLL gene. Cases harboring dmins had shorter amplified regions compared to cases with rc (4,428,112.5 bp vs. 18,265,496.9 bp; p=0.028). Moreover, we detected a positive correlation of patients having a rc and gene amplification on chromosome 11q23-25 (p<0.05). On chromosome 3q, 8/9 (88.9%) cases shared a minimal amplified region covering the EVI1 gene. In comparison to samples obtained from healthy donors (n=47), the EVI1 expression was significantly higher in cases with EVI1 amplification (87.4 vs. 0.5; p=0.048). On chromosome 21q the regions of amplifications were heterogeneous. However, we detected a minimal region containing 11 genes including ERG which was amplified in 26/29 (89.7%) patients. ERG expression data was available in 8 cases and was significantly higher compared to a control cohort of AML with normal karyotype (n=331) (729.2 vs. 229.0; p=0.05). On chromosome 8 an amplified region was identified in 15/16 cases. In 14 of these cases (87.5%) the region included MYC. TP53mut were present in 93/115 (80.9%) patients, accompanied by a TP53del in 28/93 (30.1%) cases. Interestingly, cases harboring a TP53mut had more amplified regions compared to TP53wt (3.4 vs. 1.7; p<0.001). Conclusions 1. MLL is the most frequently amplified gene in AML and MDS. 2. Patients with complex karyotypes or TP53mut harbored more amplified regions compared to patients with non-complex karyotypes and TP53wt. 3. Amplifications on 11q were more frequent in complex karyotype whereas gene amplifications on 8q were predominantly observed in non-complex karyotypes. 4. EVI1 and ERG gene amplifications lead to a higher expression of the respective genes. Disclosures: Roller: MLL Munich Leukemia Laboratory: Employment. Weber:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Zenger:MLL Munich Leukemia Laboratory: Employment. Staller:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Characterization of a de novo Supernumerary Neocentric Ring Chromosome Derived from Chromosome 7

2015 ◽  
Vol 147 (2-3) ◽  
pp. 111-117 ◽  
Author(s):  
Camille Louvrier ◽  
Grégory Egea ◽  
Audrey Labalme ◽  
Vincent Des Portes ◽  
Sophie Gazzo ◽  
...  
Keyword(s):  
Array Cgh ◽  
De Novo ◽  
Ring Chromosome ◽  
Partial Trisomy ◽  
Complete Characterization ◽  
Chromosome 7 ◽  
Oligonucleotide Array ◽  
Facial Dysmorphism ◽  
Bioinformatic Tools

Supernumerary ring chromosomes (SRC) are usually derived from regions adjacent to the centromere. Their identification may be challenging, particularly in case of low mosaicism. Here, we report on a patient who was referred for major in utero growth retardation, severe developmental delay, facial dysmorphism, cleft palate, and hypospadias. The karyotype showed a small SRC in mosaic. The combination of FISH, M-FISH and array-CGH was necessary for a complete characterization of this SRC. M-FISH revealed that the SRC originated from chromosome 7. Array-CGH performed with a 400K oligonucleotide array showed a gain in region 7q22.1q31.1 present in low mosaic. This result was confirmed by FISH using BAC probes specific for chromosome 7. The SRC was a neocentric ring derived from 7q22.1q31.1 and was found in only 8% of the cells. This is the first patient carrying a mosaic neocentric SRC derived from the long arm of chromosome 7. Our study emphasizes the need to combine different techniques and to use adapted bioinformatic tools for low-mosaicism marker identification. It also contributes to the delineation of the partial trisomy 7q phenotype.

Gain of the Centromeric Region of Chromosome 8, a New Germline Alteration In Juvenile Myelomonocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4830-4830
Author(s):  
Doris Steinemann ◽  
Tim Ripperger ◽  
Marcel Tauscher ◽  
Inka Praulich ◽  
Gudrun Göhring ◽  
...  
Keyword(s):  
High Resolution ◽  
Centromeric Region ◽  
Marker Chromosome ◽  
Normal Karyotype ◽  
Partial Trisomy ◽  
Chromosome 8 ◽  
Juvenile Myelomonocytic Leukemia ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Myelomonocytic Leukemia

Abstract Abstract 4830 Juvenile myelomonocytic leukemia (JMML) is an aggressive childhood myeloproliferative disorder characterized by the clonal hyperproliferation of myelomonocytic cells. The pathogenesis of JMML involves disruption of signal transduction through the RAS pathway, which may be an early event during leukemogenesis. Additional genetic lesions may be necessary for full malignant transformation. We applied microarray BAC/PAC- and high resolution 244k oligo-arrayCGH to bone marrow samples from 21 JMML patients in order to identify subtle genomic alterations. In 8 of13 JMML patients with normal karyotype and 2 of 8 patients with monosomy 7, additional copy number alterations were identified. A recurrent deletion of around 1.4 Mb at 17q11.2 targeting the NF1 gene was identified in 2 patients with clinical diagnosis of neurofibromatosis due to germline mutations and LOH in the tumor as described previously. In addition to the monosomy 7, one patient (D600) with a somatic mutation in PTPN11 showed an additional marker chromosome. The origin of this marker chromosome was resolved by arrayCGH. The BAC/PAC array indicated a gain of the centromeric region: arr8p12-q11.21(37,204,000-49,686,000)×3. Breakpoints were refined to 8p12-q11.21(36,673,794- 50,142,678) by high resolution oligo-aCGH. Interestingly, in patient D703 with a heterozygous CBL germline mutation and homozygosity in hematopoietic cells, we detected a nearly identical gain arr8p12-q11.21(40,076,917-49,622,319)×3 not accompanied by -7 and with slightly different breakpoints. The gain was confirmed by means of FISH using the centromere-specific probe for chromosome 8 CEP8 showing three signals. This patient was also found to have a small additional marker chromosome. In order to rule out that the marker chromosome was inherited, we performed chromosome analyses in the parents of patient D703. Both had a normal karyotype and did not carry an extra copy of the region 8p12-q11.21. However, FISH on buccal epithelial mucosa cells of the patient D703 revealed a mosaic constellation with 34% cells positive for trisomy 8. Likewise, in the second patient, the dup 8p12-q11.21 (D600) was constitutional as 38% of fibroblasts showed 3 CEP8 FISH signals. There has been a longstanding discussion as to whether mosaic trisomy 8 may be constitutional. Our findings provide evidence that at least partial trisomy 8 may indeed be present as a germline mutation. Future work is needed to determine how constitutional partial trisomy 8 might contribute to leukemogenesis in JMML with different mutational subtypes. Disclosures: No relevant conflicts of interest to declare.

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.

Molecular Delineation of Partial Trisomy 14q and Partial Trisomy 12p in a Patient with Dysmorphic Features, Heart Defect and Developmental Delay

2015 ◽  
Vol 145 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Divya Bose ◽  
Venkatesh Krishnamurthy ◽  
K.S. Venkatesh ◽  
Mohamed Aiyaz ◽  
Mitesh Shetty ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Congenital Heart ◽  
Array Cgh ◽  
Partial Trisomy ◽  
Oligonucleotide Array ◽  
Global Developmental Delay ◽  
Potential Candidate ◽  
Balanced Translocation ◽  
Dysmorphic Features ◽  
Novel Association

This study describes a molecular analysis of partial trisomy 14q and partial trisomy 12p in a 5-year-old male child presenting with dysmorphic features, congenital heart disease and global developmental delay. Chromosomal analysis of the patient with GTG bands revealed a 47,XY,+der(14)t(12;14)(p13;q22)mat karyotype; the mother's karyotype was 46,XX,t(12;14)(p13;q22). Further, oligonucleotide array- CGH studies revealed an amplification of 32.3 Mb in the 14q11.1q22.1 region, substantiating partial trisomy 14q and additionally displaying an amplification of ∼1 Mb in the 12p13.3pter region for partial trisomy 12p. This is the first study to demonstrate a novel association of partial trisomies of 14q and 12p due to a 3:1 segregation of a maternal balanced translocation involving chromosomes 12 and 14. Gene ontology studies indicated 5 potential candidate genes in the amplified regions for the observed congenital anomalies.

Ring chromosome 15: characterization by array CGH

2005 ◽  
Vol 118 (5) ◽  
pp. 611-617 ◽  
Author(s):  
Ian A. Glass ◽  
Katherine A. Rauen ◽  
Emily Chen ◽  
Jillian Parkes ◽  
Donna G. Alberston ◽  
...  
Keyword(s):  
Array Cgh ◽  
Ring Chromosome ◽  
Chromosome 15
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