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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MYCL1 has been previously mapped to 1p32. This position was in contradiction with our mapping data of 1p deletions in neuroblastoma cell lines. Using FISH on high resolution R-banded chromosomes with a YAC clone for MYCL1 we were able to reassign the gene to subband 1p34.3. This new map position is of importance for the establishment of an integrated map for chromosome 1 and the search for disease genes in this region.
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PMID:Reassignment of MYCL1 to human chromosome 1p34.3 by fluorescence in situ hybridization. 897 72

Deletions of the short arm of chromosome 1 and MYCN amplification are the most frequently encountered genetic changes in disseminated neuroblastomas and neuroblastoma cell lines. Different strategies have been followed for detection of these and other genomic changes in neuroblastoma including karyotyping, FISH, and LOH, each with its own limitations. Here we report upon the evaluation of comparative genomic hybridization (CGH) in the analysis of neuroblastoma cell lines, with the emphasis on the assessment of the reliability of CGH for the detection of distal 1p deletions. We have analyzed seven neuroblastoma cell lines for which the 1p status was previously studied in detail using FISH and LOH. Our results show that CGH allows reliable detection of distal 1p deletions, including a small interstitial deletion in cell line SK-N-AS. Furthermore, CGH also allows the detection of chromosomal imbalance which would otherwise remain undetected, and provides useful information for further molecular characterization of chromosomal imbalances.
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PMID:Comparative genomic hybridization analysis of human neuroblastomas: detection of distal 1p deletions and further molecular genetic characterization of neuroblastoma cell lines. 928 97

Cellular, cytogenetic, and molecular evidence indicates that chromosome band 1p36 is often deleted in neuroblastoma cell lines and tumours, suggesting the presence of one or more tumour suppressor genes in this region. We used a multifaceted approach to analyse the commonly deleted region, 28 distal 1p-specific polymorphic loci were used to detect loss of heterozygosity (LOH) in a panel of primary neuroblastoma tumours. Thirty-two of 122 tumours (26%) demonstrated LOH at three or more loci. In addition, a patient with a constitutional deletion of 1p36.2-.3 and two neuroblastoma cell lines with 1p36 abnormalities were characterised by FISH. When combined with the LOH data, a single consensus region of deletion was defined proximally by PLOD and distally by D1S80, a region spanning approximately five megabases. Several proposed candidate tumour suppressor genes, including ID3, CDC2L1, DAN, PAX7, E2F2, TNFR2 and TCEB3, map outside of this region; however, the transcription factor HKR3 cannot be excluded. LOH for 1p is correlated with adverse clinical and biological features and a poor prognosis, but 1p LOH is not an independent predictor of overall survival. To identify additional candidate genes, an integrated physical map of 1p35-36 is being constructed. The current map includes 445 polymerase chain reaction (PCR)-formatted markers and 608 YACs. This map will help identify region-specific transcripts by direct selection and sequencing.
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PMID:Molecular analysis of the region of distal 1p commonly deleted in neuroblastoma. 951 32

Deletions of the short arm of chromosome 1, extra copies of chromosome 17q and MYCN amplification are the most frequently encountered genetic changes in neuroblastomas. Standard techniques for detection of one or more of these genetic changes are karyotyping, FISH analysis and LOH analysis by Southern blot or PCR. Each of these techniques has its own particular limitations. More recently, comparative genomic hybridisation (CGH) was introduced for detection of genomic imbalances including deletions, duplications and gene amplification. We evaluated the sensitivity and reliability of CGH for detection of the most frequently encountered genetic changes in neuroblastoma. For this purpose a panel of well-characterised neuroblastoma cell lines as well as a series of 11 primary neuroblastomas was analysed. Our results show that CGH is a valuable tool for the genetic characterisation of neuroblastomas, both for the detection of frequently occurring genomic imbalances and for the identification of previously unnoticed genetic changes.
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PMID:Sensitive and reliable detection of genomic imbalances in human neuroblastomas using comparative genomic hybridisation analysis. 951 37

Neuroblastoma demonstrates various clinical behaviors, ranging from spontaneous regression to rapid progression regardless of the therapy used. To study the possibility that progression occurs in neuroblastoma through the accumulation of genetic aberrations, we analyzed the clonal constitution of the primary tumor and metastatic tumor samples from a stage-4 patient. Using cytofluorometry and FISH analyses, intratumor clonal heterogeneity was revealed. In the initial primary tumor sample, the nuclear DNA content indicated the coexistence of diploid and aneuploid clones, and the copy number of chromosome 1 varied from two to six. The chromosome 1 aneusomy population was composed of MYCN-amplified and 1p-deleted clones, whereas, in the chromosome 1 disomy population, coexistence of MYCN-amplified and non-amplified clones as well as 1p-deleted and 1p-intact clones was revealed. In the primary tumor after chemotherapy, the DNA-diploid component had become predominant, although the coexistence of MYCN-amplified and non-amplified clones could still be demonstrated in poorly- and well-differentiated tumor regions, respectively. This contrasted with the findings in the metastatic tumors, in which either diploid or aneuploid clone with MYCN amplification and 1p deletion dominated completely in each metastatic site. The findings suggest that the aneuploid clones had evolved from a diploid clone with MYCN amplification and a 1p deletion which, in turn, may have evolved from a diploid clone with neither MYCN nor 1p abnormality. This illustrates how various stages of multiple-step tumorigenesis may provide clues to a better understanding of the clinical heterogeneity of neuroblastoma.
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PMID:Human neuroblastoma demonstrating clonal evolution in vivo. 959 33

Comparative genomic hybridization (CGH) analysis was performed on 36 neuroblastomas of both low and high stage of disease. This study significantly increases the number of neuroblastoma tumors studied by CGH. Analysis of larger series of tumors is particularly important in view of the different clinical subgroups that are recognized for this tumor. The present data and a comparison with all published CGH data on neuroblastoma provide further insights into the genetic heterogeneity of neuroblastoma. Stage 1, 2, and 4S tumors showed predominantly whole chromosome gains and losses. A similar pattern of whole chromosome imbalances, although less frequent, was observed in stage 3 and 4 tumors, in addition to partial chromosome gains and losses. An increase in chromosome 17 or 17q copy number was observed in 81% of tumors. The most frequent losses, either through partial or whole chromosome underrepresentation, were observed for 1p (25%), 3p (25%), 4p (14%), 9p (19%), 11q (28%), and 14q (31%). The presence of 3p, 11q or 14q deletions defines a genetic subset of neuroblastomas and contributes to the further genetic characterization of stage 3 and 4 tumors without MYCN amplification (MNA) and 1p deletion. The present study also provides additional evidence for a possible role of genes at 11q13 in neuroblastoma. In a few cases, 1p deletion or MNA detected by FISH or Southern blotting was not found by CGH, indicating that the use of a second, independent technique for evaluation of these genetic parameters is recommended.
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PMID:Genetic heterogeneity of neuroblastoma studied by comparative genomic hybridization. 973 17

The mass screening (MS) of neuroblastoma has been undertaken in Japan by measuring urinary catecholamine metabolites in infants at the age of 6 months. To clarify the biological characteristics of MS-positive (MS+) tumors in infants and MS-negative (MS-)/late-presenting tumors in young children, metaphase cytogenetic and/or interphase 2-color FISH analyses using terminal 1p and pericentromeric 1q probes were performed on 246 (186 MS+ and 60 MS-) patients with neuroblastomas. The 246 tumors were classified into 4 groups on the basis of the constitution of chromosome 1; 22 tumors had disomy 1 with no 1p deletion (Dis1Norm1p); 41 tumors had disomy 1 or tetrasomy 1, all with the 1p deletion (Dis1Del1p); 164 tumors had trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells with tetrasomy 1, none with 1p deletion (Tris1Norm1p); 19 tumors with the same copy numbers of chromosome 1 as the Tris1Norm1p group, had 1p deletion (Tris1Del1p). mycn amplification was absent in the Dis1Norm1p and Tris1Del1p groups, frequent in the Dis1Del1p group (24/41), and rare in the Tris1Norm1p group (3/164) (p < 0.0001). Event-free survival at 5 years was lowest [19.5%; 95% confidence interval (CI), 5.1-33.9] in the Dis1Del1p group, highest in the Tris1Norm1p (96.3%; 95% CI, 93.5-99.2) and Tris1Del1p (94.7%; 95% CI, 84.7-104.8) groups, and intermediate but varied (54.5%; 95% CI, 33.7-75.4) in the Dis1Norm1p group (p < 0.0001). Of the MS+ tumors, 90% were Tris1Norm1p or Tris1Del1p, and 55% of the MS- tumors were Dis1Del1p. The finding that the Dis1Del1p tumors were frequent in MS- but not in MS+ tumors suggests the limited efficacy of the MS program into reducing mortality from neuroblastoma.
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PMID:Disomy 1 with terminal 1p deletion is frequent in mass-screening-negative/late-presenting neuroblastomas in young children, but not in mass-screening-positive neuroblastomas in infants. 993 30

We have characterised the DFFB gene, encoding the active subunit of the apoptotic nuclease DNA fragmentation factor (DFF40). DFFB maps to 1p36, near the imprinted putative tumour suppressor gene TP73. The DFFA gene (encoding the inhibitory DFF45 subunit) also maps to 1p36.2-36.3, and we show by FISH that DFFB lies distal to DFFA. We have also mapped a processed DFFB pseudogene to chromosome 9. DFFB itself has seven coding exons spanning 10 kb. Exhaustive mutation screening of 41 neuroblastomas and other tumours in which a 1p36 tumour suppressor gene is implicated showed no tumour-specific mutations. A coding region polymorphism was used to demonstrate uniformly biallelic expression in human fetal DFFB transcripts. Since the putative neuroblastoma tumour suppressor gene in distal 1p36 is predicted to be maternally expressed, the lack of imprinting and absence of somatic mutations in DFFB indicate that it is probably not the neuroblastoma tumour suppressor gene.
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PMID:Structure and mutation analysis of the gene encoding DNA fragmentation factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour suppressor gene. 1083 Sep 7

MYCN oncogene amplification in neuroblastoma is statistically associated with gain of chromosome segment 17q21-qter. In neuroblastoma cell lines and primary tumors with MYCN amplification in the form of homogeneously staining regions (hsrs), juxtaposition of chromosome 17 material with MYCN sequences has occasionally been reported, raising the possibility of a physical affinity between MYCN and chromosome arm 17q. We used FISH to test for association between chromosome 17 segments and MYCN in eight neuroblastoma cell lines and two neuroblastoma primary tumors known to include hsrs. Evidence of an association was found in the chromosomes of both primary tumors; in one, a MYCN hsr was inserted into a structurally abnormal chromosome 17, in the other, an hsr in 16p was shown to be flanked by 17 material. In cell line NCG, hsrs in 4q and 16p were flanked by 17q material. These observations confirm the juxtaposition of 17q material with MYCN sequences in some neuroblastomas, and imply that there may be a physical or functional relationship between these two features in MYCN amplified neuroblastoma.
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PMID:MYCN amplification and 17q in neuroblastoma: evidence for structural association. 1110 80

Tumour heterogeneity and clonal evolution at the genetic level may explain the development of malignant or resistant disease during clinical progression of neuroblastoma (NB). In this report we use 1p allelic analysis and DNA ploidy to evaluate clonal heterogeneity and clonal selection in vivo. We studied a total of 69 tumours from 29 patients with NB. To evaluate tumour heterogeneity and clonal evolution in vivo we used a panel of polymorphic allelic markers mapping to chromosome 1. 33 tumours from 12 patients (group 1) were obtained from different sites during the same surgery or at sequential surgeries without intervening chemotherapy to evaluate genetic heterogeneity. Paired samples from 10 patients (group 2) were used to evaluate clonal selection before and after chemotherapy. In 6 cases paired tumours and derived cell lines were studied. Analysis of DNA ploidy changes by karyotype, FISH and flow cytometry was performed in 15 tumours from 6 multiply recurred local-regional (LR) NB patients. Allelotype study revealed that 66% (8/12) of group 1 samples were heterogeneous, with distinct allelic patterns in tumour samples separated by time or location. In group 2 allelic patterns were different in post-chemotherapy specimens in 60% (6/10). DNA ploidy analysis showed that pre-chemotherapy samples contained 2 distinct ploidy clones, one diploid and one triploid, whereas all post-chemotherapy tumor samples were 100% diploid. These findings suggest that NB exhibits a high degree of clonal heterogeneity and clonal evolution occurs during the course of therapy and clinical progression.
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PMID:Genetic heterogeneity and clonal evolution in neuroblastoma. 1146 Oct 74


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