Analysis of chromosome 21 copy number in uncultured amniocytes by fluorescencein situ hybridization using a cosmid contig

1992 ◽  
Vol 12 (11) ◽  
pp. 931-943 ◽  
Author(s):  
Y. L. Zheng ◽  
M. A. Ferguson-Smith ◽  
J. P. Warner ◽  
M. E. Erguson-Smith ◽  
C. A. Sargent ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosome 21 ◽  
Fluorescencein Situ Hybridization ◽  
Cosmid Contig

Fluorescencein situ hybridization with a chromosome 21-specific cosmid contig: 1-day detection of trisomy 21 in uncultured mesenchymal chorionic villus cells

1994 ◽  
Vol 14 (2) ◽  
pp. 87-96 ◽  
Author(s):  
Thue Bryndorf ◽  
Britta Christensen ◽  
Yang Xiang ◽  
John Philip ◽  
Kathy Yokobata ◽  
...  
Keyword(s):  
Trisomy 21 ◽  
Chorionic Villus ◽  
Chromosome 21 ◽  
Fluorescencein Situ Hybridization ◽  
Cosmid Contig

PSVIII-10 Genome-wide CNV analysis unravels a deletion associated with parasite resistance in Florida native sheep

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 243-244
Author(s):  
Brittany N Diehl ◽  
Andres A Pech-Cervantes ◽  
Thomas H Terrill ◽  
Ibukun M Ogunade ◽  
Owen Rae ◽  
...  
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Chromosome 21 ◽  
Trend Test ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Parasite Resistance ◽  
Association Testing ◽  
Genome Wide ◽  
Native Sheep

Abstract Florida Native sheep is an indigenous breed from Florida and expresses superior parasite resistance. Previous candidate and genome wide association studies with Florida Native sheep have identified single nucleotide polymorphisms with additive and non-additive effects associated with parasite resistance. However, the role of other potential DNA variants, such as copy number variants (CNVs), controlling this complex trait have not been evaluated. The objective of the present study was to investigate the importance of CNVs on resistance to natural Haemonchus contortus infections in Florida Native sheep. A total of 200 sheep were evaluated in the present study. Phenotypic records included fecal egg count (FEC, eggs/gram), FAMACHA score, and packed cell volume (PCV, %). Sheep were genotyped using the GGP Ovine 50K SNP chip. The copy number analysis was used to identify CNVs using the univariate method. A total of 170 animals with CNVs and phenotypic data were used for the association testing. Association tests were carried out using single linear regression and Principal Component Analysis (PCA) correction to identify CNVs associated with FEC, FAMACHA, and PCV. To confirm our results, a second association testing using the correlation-trend test with PCA correction was performed. Significant CNVs were detected when their adjusted p-value was < 0.05 after FDR correction. A deletion CNV in chromosome 21 was associated with FEC. This DNA variant was located in intron 2 of RAB3IL gene and overlapped a QTL associated with changes in eosinophil number. Our study demonstrated for the first time that CNVs could be potentially involved with parasite resistance in this heritage sheep breed.

Identification of Aberrantly Regulated Genes through Comparison of Genome-Wide Expression Profiles and Karyotype in Hyperdiploid >50 Chromosomes Pediatric Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 420-420
Author(s):  
Christian Flotho ◽  
Susana C. Raimondi ◽  
James R. Downing
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Expression Profiles ◽  
Chromosome 21 ◽  
Small Subset ◽  
Specific Gene ◽  
Expression Levels ◽  
Number Of Genes ◽  
The Mean ◽  
Gene Expression Levels

Abstract We have demonstrated that expression profiling of leukemic blasts can accurately identify the known prognostic subtypes of ALL, including T-ALL, E2A-PBX1, TEL-AML1, MLL rearrangements, BCR-ABL, and hyperdiploid >50 chromosomes (HD>50). Interestingly, almost 70% of the genes that defined HD>50 ALL localized to chromosome 21 or X. To further explore the relationship between gene expression and chromosome dosage, we compared the expression profiles obtained using the Affymetrix U133A&B microarrays of 17 HD>50 ALLs to 78 diploid or pseudodiploid ALLs. Our analysis demonstrated that the average expression level for all genes on a chromosome could be used to predict chromosome copy numbers. Specifically, the copy number for each chromosome calculated by gene expression profiling predicted the numerical chromosomal abnormalities detected by standard cytogenetics. For chromosomes that were trisomic in HD>50 ALL, the mean chromosome-specific gene expression level was increased approximately 1.5-fold compared to that observed in diploid or pseudodiploid ALL cases. Similarly, for chromosome 21 and X, the mean chromosome-specific gene expression levels were increased approximately 2-fold, consistent with a duplication of the active X chromosome and tetrasomy of chromosome 21, a finding verified by standard cytogenetics in >90% of the HD>50 cases. These finding indicate that the aberrant gene expression levels seen in HD>50 ALL primarily reflect gene dosages. Importantly, we did not observe any clustering of aberrantly expressed genes across the duplicated chromosomes, making regional gain or loss of genomic material unlikely. Paradoxically, however, a more detailed analysis revealed a small but statistically significant number of genes on the trisomic/tetrasomic chromosomes whose expression levels were markedly reduced when compared to that seen in diploid or pseudodiploid leukemic samples. Using the Statistical Analysis of Microarrays (SAM) algorithm we identified 20 genes whose expression was reduced >2-fold despite having an increase in copy number. Interestingly, included within this group are several known tumor suppressors, including AKAP12, which is specifically silenced by methylation in fos-transformed cells, and IGF2R and IGFBP7, negative regulators of insulin-like growth factor signaling. In addition to the silencing of a small subset of genes, we also identified 21 genes on these chromosomes whose expression levels were markedly higher (>3-fold) than would be predicted solely based on copy number. Although the mechanism responsible for their increased expression remains unknown, included in this group are four genes involved in signal transduction (IL3RA, IL13RA1, SNX9, and GASP) and a novel cytokine, C17, whose expression is normally limited to CD34+ hematopoietic progenitors. Taken together, these data suggest that aberrant growth in HD>50 ALL is in part driven by increased expression of a large number of genes secondary to chromosome duplications, coupled with a further enhanced expression of a limited number of growth promoting genes, and the specific silencing of a small subset of negative growth regulatory genes. Understanding the mechanisms responsible for the non-dosage related changes in gene expression should provide important insights into the pathology of HD>50 ALL.

A High Resolution Analysis of Chromosome 21 Amplification In Myeloid Malignancies Reveals An Association with a Specific Cytogenetic Subgroup and Enhanced ERG Gene Expression.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1687-1687
Author(s):  
Hideki Makishima ◽  
Hideki Muramatsu ◽  
Asahito Hama ◽  
Ramon V. Tiu ◽  
Yuka Sugimoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
High Resolution ◽  
Copy Number ◽  
Trisomy 21 ◽  
Chromosome 21 ◽  
Mrna Levels ◽  
Myeloid Malignancies ◽  
Runx1 Gene ◽  
Cd34 Cells

Abstract Abstract 1687 Genetic alterations including chromosomal translocation, somatic mutation, and gene amplification are thought to play a key role in oncogenesis. Gains of whole or segmental chromosome 21 (Ch21) are observed in many types of myeloid malignancies and are often associated with acute megakaryoblastic leukemia (AMKL). In Down syndrome, transient abnormal myelopoiesis and acute lymphoblastic leukemia can be observed, but the prevalence of AMKL is striking. In rare Down syndrome patients, a subcytogenetic Ch21 minimal amplified region is observed and always found to include ERG as well as the RUNX1 gene locus. Recently, gain of ERG gene copy number has been demonstrated to induce leukemia in mouse models and mutations in RUNX1 have been reported in patients with myeloid malignancies with somatic trisomy 21. The pathogenic gene(s) driving malignant disease in congenital and/or somatic gain of Ch21 are poorly understood. We applied high resolution single nucleotide polymorphism array (SNP-A) to study whether small copy number gains are present on Ch21, which cannot be seen by metaphase cytogenetics. We also tested for potential synergistic karyotypic abnormalities in the patients with gain of Ch21 gene segments. We screened a large cohort of 522 patients with myeloid malignancies by SNP-A platform, and detected 36 events that included whole or partial amplification of Ch21 in 32 cases (6%). The affected length was between 215,063 and 46,944,323 bp and the average was 30,732,002. These include 13 congenital lesions (AMKL evolving in Down syndrome), and 23 somatic alterations. Among the AMKL cohort of 34 cases, gains of Ch21 were observed in 15/25 (60%) juvenile and 2/9 (22%) adult cases. A minimal consensus amplification region was defined from nt38637816 to nt38852879 on Ch21 and this region included ERG. Amplification of ERG was identified in 30/36 of the Ch21 gain lesions studied. Although we sequenced all exons of the ERG gene in all cases with Ch21 gain, no mutation was detected. Based on the possibility that gene amplification leads to increased gene expression, ERG mRNA levels were investigated. CD34+ cells showed the highest ERG expression among hematopoietic cell types. When CD34+ cells from acute myeloid leukemia (AML) patients with somatic trisomy 21, with normal copy of Ch21 and healthy donors were investigated by real time PCR, relative expression of ERG was the highest in trisomy 21 patients among three groups. Based on our previous work and that of others, we tested the mutational status of RUNX1 in the 23 cases with Ch21 amplification that included RUNX1. Mutations were found in 2/23 (9%) accompanied by trisomy 21. No mutation was found in patients with Down syndrome. In one mutant case, a homozygous missense mutation, (L56S) was identified and associated with uniparental trisomy that included RUNX1. The second mutant case (W106L) was in a patient with a 45,XY,-7,i(21)(q10) karyoptype. The mutation was duplicated but was not associated with loss of heterozygosity (LOH). When RUNX1 gene expression in the cases with and without trisomy 21 using CD34 positive bone marrow cells was investigated, no significant difference in relative RUNX1 mRNA levels between trisomy 21 and cases with diploid Ch21 was found. Finally, we evaluated whether additional chromosomal lesions were associated with a gain of Ch21 gene segments. Recurrent losses were detected on chromosome 1, 2, 3, 5, 7, 9, and 17. Deletions of 5q were frequent in the cases with somatic gain of Ch21 (47%; 8/17), while no del5q was detected in the cases with Down syndrome. Conversely, LOH17p (3 uniparental disomies (UPDs) and 2 deletions) was found in both somatic and congenital cases (5/32), with one case of deletion17p associated with a hemizygous p53 mutation. In addition, UPD11q was accompanied by a CBL homozygous mutation in a RAEB case with somatic trisomy 21. Del7q was also observed in both groups (4 in somatic and 3 in congenital cases), including a 7q36.1 microdeletion associated with EZH2 in AMKL with Down syndrome. In sum, our study demonstrates that high resolution SNP-A analysis focused on Ch21 gene segments revealed frequent cryptic somatic gain lesions and a uniparental trisomy. ERG was the sole gene located in the minimally shared gain lesions and is overexpressed in a wild type form in AML cases with somatic trisomy 21. RUNX1 mutations were found in 3 or 2 identical alleles of somatic trisomy 21 cases but are absent in most cases of trisomy 21. Disclosures: No relevant conflicts of interest to declare.

The Impact of Constitutional Copy Number Variants in Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 496-496
Author(s):  
Matthew W Jenner ◽  
David C Johnson ◽  
Paola E Leone ◽  
Brian A Walker ◽  
David Gonzalez ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Change ◽  
Copy Number Variations ◽  
Genomic Variation ◽  
Chromosome 21 ◽  
Nucleotide Polymorphisms ◽  
Copy Number Changes ◽  
The Impact ◽  
First Time ◽  
Tumor Dna

Abstract Single nucleotide polymorphisms (SNPs) have been long regarded as being important in determining variation and disease predisposition. Recently, chromosomal structural variation in the form of deletions, insertions and duplifications have been identified frequently in the genome of the general population. Such copy number variations (CNVs) have been shown to contribute to a range of human diseases. In recent studies we have utilized Affymetrix 50K and 500K arrays to identify acquired copy number change in myeloma tumor samples. In those studies we had access to paired constitutional DNA and in the present study have been able to report for the first time a CNV map of the constitutional genome of myeloma patients. Affymetrix 500K mapping arrays were used to identify copy number changes in 63 paired samples using DNA from peripheral blood and CD138 selected plasma cells. Tumor samples were analyzed in CNAG using both a paired and unpaired analysis to distinguish between inherited and acquired copy number change. Constitutional DNA was analyzed by both CNAG and GEMCA using 90 Caucasian samples from the Hapmap database as a reference set. For maximum calling accuracy, only those regions identified by both algorithms were called as CNVs. As with similar studies, overlapping CNVs identified using this approach were merged to generate a list of CNV regions (CNVRs) characteristic of the constitutional DNA of these myeloma cases. Using this approach, we identified 292 CNVs across 63 cases, with a median of 4 regions per sample. There were 155 discrete CNVRs, of which 46 were recurrent. The recurrent CNVRs were found most frequently in the pericentric regions of chromosome 14 and 15 in keeping with other studies. We then compared these recurrent CNVRs with a comparable dataset of normal individuals generated using Affymetrix 500K arrays. In this analysis, 25/46 recurrent CNVRs in the myeloma cases were novel. The two most frequent novel CNVRs in the myeloma cases were gains on chromosome 21 and 15. We also compared the characteristics of the constitutional CNVs with the acquired copy number changes in the corresponding tumor samples and identified that the constitutional CNVs were generally considerably smaller. However, using unpaired analysis it was possible to determine the presence of the constitutional CNV in the tumor sample, providing validation of the CNVs. We were also able to demonstrate that acquired copy number change in the tumor cells can either exaggerate or ameliorate the effect of the inherited CNV in the tumor genome, such as cases with acquired trisomy 15 and deletion or gain of regions of 15q in the constitutional DNA. These findings also reinforce the need for paired non-tumor DNA when undertaking copy number analysis of tumor DNA using SNP arrays. In this study we have been able to identify for the first time the presence of CNVs in the constitutional genome of individuals with myeloma. We have been able to systematically catalogue these CNVRs. These results provide the basis for future studies aimed at identifying how this type of genomic variation may influence the development of and outcome of myeloma and a broad range of other hematological conditions.

RUNX1 Deletions Are a Novel Mechanism of Loss of Function in AML and Are Associated with Adverse Cytogenetics.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2517-2517
Author(s):  
Claudia Haferlach ◽  
Vera Grossmann ◽  
Melanie Zenger ◽  
Wolfgang Kern ◽  
Torsten Haferlach ◽  
...  
Keyword(s):  
Copy Number ◽  
De Novo ◽  
Chromosome 21 ◽  
Prognostic Impact ◽  
Complex Karyotype ◽  
Loss Of Function ◽  
Array Data ◽  
Runx1 Gene ◽  
Equity Ownership ◽  
Wbc Count

Abstract Abstract 2517 Background: RUNX1 is a crucial hematopoietic transcription factor located on the long arm of chromosome 21 (21q22). Three types of acquired alterations of the RUNX1 gene have been described in AML so far: 1. translocations leading to fusion genes such as t(8;21)(q22;q22)/RUNX1-RUNX1T1 2. molecular mutations, which usually lead to loss of normal RUNX1 function, and 3. amplifications, which are predominately found in AML with complex karyotype. Another possible mechanism that causes loss of function is a partial or complete deletion of the gene. Aim: To clarify whether RUNX1 is also affected by partial or complete deletions in AML. Patients and Methods: We screened 623 AML patients (pts) for RUNX1 deletions (del) by interphase fluorescence in situ hybridization using probes spanning the complete RUNX1 gene (MetaSystems, Altlussheim, Germany). The cohort comprised 472 de novo, 85 secondary (s-AML), and 66 therapy-related AML (t-AML). Median age was 67.3 yrs (range: 18 to 91.5 yrs). For all pts cytogenetics was available and categorized according to refined MRC criteria (Grimwade et al. Blood 2010). Cytogenetics were favorable in 164, intermediate in 210 and adverse in 249 pts, respectively. RUNX1 mutation analysis was performed in 252 cases. In addition, 19 pts with RUNX1 del were analyzed by genomic arrays (Human CGH 12×270K Whole-Genome Tiling Array, Roche NimbleGen, Madison, WI (n=12); SNP 6.0 arrays, Affymetrix, Santa Clara, CA (n=7)). Results: Frequency and clinical characteristics: In 57/623 (9.1%) cases deletions affecting RUNX1 were identified. The frequency of RUNX1 del did not vary significantly between de novo (8.9%), s-AML (11.8%) and t-AML (7.6%). However, RUNX1 del were more frequent in pts with adverse cytogenetics (18.1%) compared to intermediate (5.7%) or favorable cytogenetics (0%, p<0.0001). In contrast, RUNX1 mutations (mut) were more frequent in intermediate (26.1%) as compared to favorable (0%) and unfavorable cytogenetics (10.5%, p=0.003). Pts harboring RUNX1 del were significantly older than those with 2 RUNX1 copies (mean: 70.0 vs 61.6 yrs, p<0.0001) and showed lower WBC count (mean: 13,225 vs 21,419/μl, p=0.010), while no difference was observed with respect to hemoglobin level and platelet count. Cytogenetics: 38/57 (66.7%) pts with RUNX1 del harbored a complex karyotype, one case showed a normal karyotype while a variety of different abnormalities were found in the remaining 18 pts. Type of cytogenetic alteration: In 5 cases one RUNX1 allele was lost due to monosomy 21. In two cases a deletion of the long arm of chromosome 21 was cytogenetically visible. 29 pts showed derivative chromosomes 21 resulting from unbalanced translocations or duplications of the long arm of chromosome 21. Ring chromosomes 21 were found in 3 cases. In 7 pts a translocation involving 21q22 was identified. 11 cases with a RUNX1 del showed cytogenetically normal chromosomes 21. Remarkably, 6 of these 11 pts showed a trisomy 21. RUNX1 mutations: 36 pts with RUNX1 del were also evaluated for RUNX1 mut. In 7 pts (19.4%) a RUNX1 mut in the remaining allele was detected. Thus, the mutation frequency did not differ from pts without RUNX1 del (40/216, 18.5%). Genomic array data: The size of the deletion on chromosome 21 varied between 258 kb and 11,792 kb (median: 1,987 kb). In one case a homozygous RUNX1 deletion was detected. Based on array data pts with RUNX1 del were subdivided into two groups: The first group comprised 7 pts with a non-complex karyotype and an interstitial deletion on chromosome 21 encompassing RUNX1. Secondly, in 12 pts with RUNX1 del and a complex karyotype array data revealed between 2–16 changes in copy number state on chromosome 21. Interestingly, in 4/12 (30%) cases the ERG gene, located 2.6 Mb telomeric to RUNX1, was amplified. Conclusions: 1. Partial or complete deletions of RUNX1 are frequent recurrent genetic events in AML. 2. They are associated with adverse cytogenetics, lower WBC count and are more frequent in elderly patients. 3. Loss of one RUNX1 copy results either from clear-cut interstitial deletions on chromosome 21 or occurs based on highly rearranged chromosomes 21 showing several changes in copy number states accompanied by gains and losses of several regions on chromosome 21. Whether the pathogenetic impact of RUNX1 del is comparable to RUNX1 mut and if they have prognostic impact independent of cytogenetics remains to be studied. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership. Grossmann:MLL Munich Leukemia Laboratory: Employment. Zenger:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership.

scholarly journals Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects

2017 ◽  
Vol 8 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Benjamin L. Rambo-Martin ◽  
Jennifer G. Mulle ◽  
David J. Cutler ◽  
Lora J. H. Bean ◽  
Tracie C. Rosser ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Congenital Heart Defects ◽  
Copy Number ◽  
Congenital Heart ◽  
Heart Defects ◽  
Copy Number Variants ◽  
Chromosome 21

scholarly journals Deciphering the Chronology of Copy Number Alterations in Multiple Myeloma (MM): What Comes First?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3171-3171
Author(s):  
Anil Aktas Samur ◽  
Mehmet Kemal Samur ◽  
Stephane Minvielle ◽  
Florence Magrangeas ◽  
Masood A. Shammas ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Copy Number ◽  
Early Stage ◽  
Chromosome 21 ◽  
Chromosome 15 ◽  
Newly Diagnosed ◽  
Copy Number Alterations ◽  
Advisory Committees ◽  
Equity Ownership ◽  
1Q Gain

Abstract Multiple Myeloma (MM) is characterized by genomic heterogeneity with copy number alterations (CNA) as one of the most prominent genomic perturbation. Hyperdiploidy involving chromosomes 3,5,7,9,11,15,19, and 21 is observed in nearly half of the patients, however the chronological sequence of their occurrence during MM development remains unknown. Here, we have acquired one of the largest genomic datasets from 647 patients that combines data from monoclonal gammopathy of undermined significance (MGUS) to newly diagnosed MM (336 newly diagnosed MM, 147 smoldering MM (SMM) and 164 MGUS) to characterize when and in what sequence CNA occurs in MM development. We deduce the order of CNA events by identifying their pattern of clonality basically inferring that clonal genomic change suggest its origin at an earlier stage of the disease. In hyperdiploid MM (HMM), gains in chromosome 19 (95%), 15 (90%) and 9 (90%) are the most frequent events, followed by gains in 5,11,3,7 and 21. Based on the clonality assessment the gain of chromosome 15 is the first and most frequent clonal/near clonal event, observed in 95% of HMM patients followed by Chromosome 9. Surprisingly, although chromosome 19 gain is the most frequent event overall, its clonal occurrence was lower than clonal chromosome 15 gain. More than 96% of HMM samples had concurrent gains in at least 2 of the 3 most frequent chromosomes (9,15 and 19). Moreover, less frequent events such as chromosome 21 gain, 18p gain, and 1q gain showed higher frequency of clonal/near clonal occurrence compared to other events indicating that when these events occur they are early events. Majority of the deletions occur as late subclonal events with few or none observed as clonal events. In the nonhyperdiploid MM (NHMM), del13, gain of 1q and gain of 11 had the highest frequency of clonal occurrence. Most were clonal events signifying its importance in the early stages of the disease. As all MM originates from its precursor conditions, MGUS and SMM, clonal and likely early CNAs in MM, must also exist in MGUS and SMM. So, we next investigated genomic data from SMM and MGUS for the occurrence of clonal events observed in MM. We confirmed same patterns for top MM-related CNA events in SMM and MGUS and observed no significant difference (p=0.1) between the number of events in hyperdiploid groups in MM (median=10, IQR= [8-12]) and SMM (median=9, IQR= [7-11]).To further confirm the analysis, we calculated an average clonality score for each chromosomal alteration using a 1 to 5 clonality index (1 being clonal 5 being low subclonal) in MM, SMM and MGUS and observed that similar clonal trisomies median=5, IQR=[4-6] are observed in both HMM and hyperdiploid MGUS; and that not all trisomies are required or occur at the same time. With occurrence in over 96% of cases trisomy involving chromosome 15 is central to the development of MGUS and later on MM. This is closely followed by trisomy of 9, and 19. Gain of chromosome 21 is also an early event. Major events like deletion 13 and 1q gain occur relatively later than first hyperdiploid events. NHMM on the other hand is well known to have clonal IgH-associated translocation as an initiating feature which is also observed in SMM and MGUS. However, different from HMM, it shows only few CNAs at an early stage and does not accumulate frequent additional alterations. The only exception to this rule is a deletion group observed in HMM, NHMM and SMM but not MGUS. In this deletion in over 10 whole chromosome or its p or q arm are involved as subclonal events. Its absence in MGUS suggests them to be a later event in MM development. On the other hand, number of deletions are observed at the same locations in both hyperdiploid and non-hyperdiploid groups with similar frequency. Moreover, similarity of events in this deletion groups strongly suggest that in sub group of both HMM and NHMM a similar process may be operative to induce such deletions. Our results also highlight that for both HMM and NHMM groups the major copy number events are not adequate for eventual malignant transformation since only a small fraction of MGUS patients progress to MM. Here, we describe the time line of initial copy number alterations observed in MM and confirm their early occurrence using data from a unique early stage plasma cell cases. Similarities between stages show that large scale DNA alterations happen early however some copy number hotspots are enriched over the time which could be important for disease progression. Disclosures Moreau: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Anderson:Bristol Myers Squibb: Consultancy; C4 Therapeutics: Equity Ownership, Other: Scientific founder; Gilead: Membership on an entity's Board of Directors or advisory committees; OncoPep: Equity Ownership, Other: Scientific founder; Millennium Takeda: Consultancy; Celgene: Consultancy. Munshi:OncoPep: Other: Board of director.

Sign in / Sign up

Export Citation Format

Share Document