DELETIONS OF CHROMOSOME 20q AND THE PATHOGENESIS OF MYELOPROLIFERATIVE DISORDERS

Asimakopoulos, Fotios A.; Green, A R

doi:10.1046/j.1365-2141.1996.d01-1896.x

Cited by 92 publications

(36 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is consistent with the frequent deletions on chromosome 20q observed in cytogenetic studies of MDS. 20 The FAL was calculated as the ratio of chromosomal arms…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Allelotype analysis of the myelodysplastic syndrome

et al. 2000

View full text Add to dashboard Cite

Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders found predominantly in the elderly. The molecular mechanisms underlying the development of MDS remain obscure. In order to begin to identify tumor suppressor genes involved in these disorders, we performed a detailed microsatellite allelotype of chromosomal deletions associated with MDS. DNAs from both bone marrow and peripheral blood of 32 MDS patients were studied using 84 highly informative microsatellite markers on all autosomal arms, excluding the short arms of the acrocentric chromosomes. A high percentage of loss of heterozygosity (LOH) was identified on chromosome 5q (40% of informative cases), 7q (45%), 17p (23%) and 20q (20%), which corresponds to the most common cytogenetic abnormalities reported in MDS. In addition, a high incidence of LOH (у20%) was observed on chromosomal arms which had not been previously reported including 1p (36%), 1q (35%), and 18q (23%). This extensive allelotype analysis focuses attention on several novel genomic regions that probably contain novel tumor suppressor genes whose loss of function contributes to the development of MDS. Leukemia (2000) 14, 805-810.

show abstract

“…This is consistent with the frequent deletions on chromosome 20q observed in cytogenetic studies of MDS. 20 The FAL was calculated as the ratio of chromosomal arms…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have identified deletions at chromosome 1q21-22 in cancers of the breast, 24 colon, 10 lung, 12 and stomach. 20 Also, LOH has been reported at 1q23-32 in breast cancer. 25 Translocation between 1q and 5q, 26 trisomy 1q, 27 and either rearrangement or duplication of chromosome 1q 28 have been observed in MDS.…”

Section: Discussionmentioning

confidence: 99%

Allelotype analysis of the myelodysplastic syndrome

et al. 2000

View full text Add to dashboard Cite

show abstract

“…In MDS, isolated 20q deletions were found to be prognostically favorable [27][28][29], whereas in the MPN an impact on prognosis so far was not determined [35].…”

Section: Discussionmentioning

confidence: 99%

Distribution of cytogenetic abnormalities in myelodysplastic syndromes, Philadelphia negative myeloproliferative neoplasms, and the overlap MDS/MPN category

et al. 2009

View full text Add to dashboard Cite

(2008), chronic myeloid malignancies are divided in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), and overlap MDS/MPN cases. From morphological aspects, these categories show overlaps. To evaluate whether these morphological similarities have genetic parallels, we investigated 1,851 cases with suspected/confirmed myelodysplastic or myeloproliferative diseases by chromosome banding and molecular analyses. Cytogenetics revealed aberrant karyotypes in 354 patients (19.1% of the original cohort) who were the basis of further analysis. The distribution of chromosomal aberrations differed significantly between categories. Isolated +9 and gain of 9p were exclusively observed in MPN (+9: 10/93; 11%; p<0.001; +9p: 6/93; 7% of all aberrant MPN cases) but were not detected in MDS or MDS/MPN (p=0.001). Isolated del(5q) (p=0.002), −7 in combination with other aberrations (p=0.016), and complex aberrations (p=0.003) were 2.9-to 7.5-fold more frequent in MDS than in MPN. Trisomies 8 and 21 and del(20q) were comparably frequent in both subgroups. Interestingly, the MDS/MPN overlap cohort showed a higher frequency of −7 accompanied by other aberrations (3/17; 18% of all aberrant cases; p=0.001), i(17)(q10) (2/17; 12%; p=0.013), and +21 (2/17; 12%; p=0.013) when compared to MPN or MDS only. These differences support the category for MDS/MPN within the new WHO classification. Overlaps between the diverse disorders were seen also for the JAK2V617F (MPN 66/89; 74%; MDS/MPN 4/14; 29%; MDS 2/63; 3%) and NRAS mutations (MDS 2/67; 3%; MPN 2/4; MDS/MPN 1/1). In conclusion, cytogenetics and molecular genetics show overlaps in varying proportions of MDS and MPN cases which might indicate common pathways in their etiology. Some markers are strongly associated with one of these disorders and can be helpful for differential diagnosis especially in difficult cases.

show abstract

“…Chronic myeloid malignancies are associated with deletions of 20q (10)(11)(12). The 20q minimal deleted region spans 1.9 Mb and contains multiple genes, including L3MBTL1 (13), a transcriptional repressor (14)(15)(16) homologous to the Drosophila tumor-suppressor gene lethal(3) malignant brain tumor (17,18).…”

Section: Introductionmentioning

confidence: 99%

Cooperativity of imprinted genes inactivated by acquired chromosome 20q deletions

Aziz¹,

Baxter²,

Edwards³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

Large regions of recurrent genomic loss are common in cancers; however, with a few well-characterized exceptions, how they contribute to tumor pathogenesis remains largely obscure. Here we identified primaterestricted imprinting of a gene cluster on chromosome 20 in the region commonly deleted in chronic myeloid malignancies. We showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis, 2 lineages commonly affected in chronic myeloid malignancies, with distinct consequences in each lineage. We demonstrated that L3MBTL1 and SGK2 collaborated in the transcriptional regulation of MYC by influencing different aspects of chromatin structure. L3MBTL1 is known to regulate nucleosomal compaction, and we here showed that SGK2 inactivated BRG1, a key ATP-dependent helicase within the SWI/ SNF complex that regulates nucleosomal positioning. These results demonstrate a link between an imprinted gene cluster and malignancy, reveal a new pathogenetic mechanism associated with acquired regions of genomic loss, and underline the complex molecular and cellular consequences of "simple" cancer-associated chromosome deletions.

show abstract

DELETIONS OF CHROMOSOME 20q AND THE PATHOGENESIS OF MYELOPROLIFERATIVE DISORDERS

Cited by 92 publications

References 0 publications

Allelotype analysis of the myelodysplastic syndrome

Allelotype analysis of the myelodysplastic syndrome

Distribution of cytogenetic abnormalities in myelodysplastic syndromes, Philadelphia negative myeloproliferative neoplasms, and the overlap MDS/MPN category

Cooperativity of imprinted genes inactivated by acquired chromosome 20q deletions

Contact Info

Product

Resources

About