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

It is clear that there are at least two classes of cancer-related genes. The more characterized of these are the oncogenes, whose activation appears to play a major role in human neoplasia. There are now two families of oncogenes, the myc and ras families, whose cooperation seems capable of transforming normal cells in culture to tumorigenic cells. As such, they appear to form complementation groups with immortalizing and transforming properties, respectively. Moreover, the oncogenes can be subclassified as tyrosine kinases or kinase related, GTP binding proteins, growth factors or growth factor receptors or nuclear proteins. More than 20 viral oncogenes have been identified, for which more than 30 proto-oncogenes or pseudogenes exist in the human genome. Many of these have been cloned, characterized to some extent, and mapped to particular chromosomes or regions of chromosomes. Further, more than 20 additional putative oncogenes or transforming genes have been identified by tumor DNA transfection studies or at sites of integration or translocation for which no viral transforming gene cognates exist. Oncogenes can be activated by increased or unregulated expression, increased copy number (duplication, amplification), or somatic mutation resulting in a protein with increased oncogenic potential. Examples of all of these mechanisms can be found in several specific human cancers or leukemias. The cytogenetic correlate of enhanced expression is a translocation between two chromosomes at specific breakpoints with no net loss of genetic material (e.g., increased c-myc expression resulting from the 8;14 translocation in Burkitt's lymphoma). The phenomenon of increased gene copy number can sometimes be visualized as trisomy or tetrasomy for a particular chromosome but more dramatically as the development of extrachromosomal DMs or as chromosomally integrated HSRs (e.g., the N-myc gene amplification seen in neuroblastoma). Finally, certain somatic mutations can be associated with translocations (e.g., the bcr/abl fusion product created as a result of the 9;22 translocation in chronic myelogenous leukemia), but they are more commonly submicroscopic (as characterized by point mutations in the ras gene family). Evidence is accumulating for a second class of cancer-related genes whose absence or inactivation is associated with tumorigenesis. These genes are associated at the cytogenetic level with chromosomal deletions, in which the breakpoints may be variable, but specific, common regions are consistently deleted.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The involvement of oncogenes and suppressor genes in human neoplasia. 331 93

Chromosomes with regions rich in mitotic chiasmata in Bloom syndrome (1,3,6,11,12,17,19, and 22) have been compared for various parameters to similar-sized chromosomes 2, 4, 7, 10, 9, 18, 20, and 21 with the following results: (1) The number of genes localized on the test chromosomes is significantly higher (248) than that in the control chromosomes (133). (2) The number of trisomic abortions is significantly lower (45) for the test chromosomes than for the control chromosomes (140). (3) Homogeneously stained regions in neuroblastoma lie at chiasma-containing regions on chromosome arms 1p, 6p, 17q, and 19p or q. (4) The average chiasma density of regions with at least one oncogene is 2.414, whereas that of regions containing no known oncogene is 1.137; however, the difference is not statistically significant. The association of constant cancer chromosome breaks is also in the positive direction, but is not statistically significant. Our tentative conclusion is that the chiasma-rich regions which are Q-dark and early-replicating, and therefore assumed to contain active "housekeeping" genes are extended in interphase. Thus they are available for mitotic crossing-over. In the trisomic state they act as trisomy lethals, leading to early abortions. Being gene-rich they are more likely to contain oncogenes which is reflected also in their agreement with cancer breakpoints. The very high incidence of cancer in Bloom syndrome is a further indication of the possible association of cancer-related phenomena and mitotic crossing-over.
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PMID:Mitotic chiasmata, gene density, and oncogenes. 399 47

The proband in this study had multiple congenital malformations and a constitutional 46,XY,-13, + der(13),t(13;15)(q34;q23)mat chromosome complement. A bone marrow aspirate revealed neuroblastoma, and cytogenetic studies on tumor cells revealed, in addition to the partial trisomy #15 and probable partial monosomy #13, hypotetraploidy with a mean chromosome number of 82-84, including 3 or 4 copies of each autosome, 2 X chromosomes, no Y chromosome, and a marker. Translocations involving chromosomes #1, #2, #3, #7, and #14 were present, along with multiple double minutes. The possibility that the inherited partial trisomy #15 (and/or partial chromosome #13 monosomy) predisposed to neuroblastoma and additional chromosome changes in this tumor is discussed.
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PMID:Inherited partial trisomy #15 complicated by neuroblastoma. 669 36

A 20-week-old foetus with 8p trisomy, as the unbalanced product of a maternal 7q/8p translocation (karyotype: 46,XX,t(7;8)(q34,p12) is reported. Internal malformations include agenesis of the gall-bladder, left heart hypoplasia and pancreas annulare. Moreover, histologic examination revealed a "neuroblastoma in situ". The possible etiologic relationship between the neuroblastoma and the chromosomal abnormality is briefly discussed.
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PMID:8p trisomy in a malformed foetus. 698 67

Chromosome I abnormalities are indicators of prognosis in neuroblastoma (NB) but are not yet routinely exploited because conventional methods are technically demanding. We evaluated the pertinence of interphase cytogenetics fluorescence in situ hybridization (FISH) for the analysis of chromosome I in NB, compared with conventional methods. Deletion of Ip was detected in 8 of 9 cell lines analyzed by both FISH and restriction fragment length polymorphism (RFLP), but was evidenced in only 2 cases by conventional cytogenetics, painting analysis being required to reveal the other cases. The chromosome I number evaluated by FISH reflected the total chromosome modal number obtained by cytogenetics. Twenty-eight specimens obtained from ultrasound-guided punctures, surgical biopsies of the primary tumor and bone-marrow aspirates were studied by FISH on frozen cytocentrifuged smears; 12 had a chromosome I trisomy and 16 a disomy. Requirements for a reliable control analysis of Ip deletion by RFLP were met in only 23 cases. The retention of 2 alleles was observed in 15 cases and Ip deletion in 7, by both techniques. In one case, an interstitial deletion of Ip was evidenced only by RFLP, and one of 5 cases analyzed only by FISH had a Ip deletion. Although FISH might be improved by using additional probes, it presents major advantages for routine exploitation. Determining Ip deletion in individual cells makes it possible to analyze small and heterogeneous tumoral specimens; the technique requires only a few hours and can easily be standardized in non-specialized laboratories. The number of chromosome I homologues per cell might serve as a rapid screening for ploidy.
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PMID:Sensitive detection of numerical and structural aberrations of chromosome 1 in neuroblastoma by interphase fluorescence in situ hybridization. Comparison with restriction fragment length polymorphism and conventional cytogenetic analyses. 770 46

We present three probands with partial trisomies 2p21-23 due to ins(4;2)(q21;p21p23) pat, 2p23-pter due to t(2;4)(p23;q35)mat, and 2p21-pter due to t(2;11)(p21;q23.3)mat. More than 50 cases of partial trisomy 2p have been reviewed and some abnormalities, unusual for most other types of structural autosomal imbalance, have been found in patients with inherited forms of 2p trisomy and in their non-karyotyped sibs. Neural tube defects (anencephaly, occipital encephalocele, and spina bifida) were found in five probands and 4/6 affected non-karyotyped sibs. The only triplicated segment common to all was 2p24. Different forms of "broncho-pulmonary a/hypoplasia" (including two cases of lung agenesis) were described in four patients (overlapping triplicated segment was 2p21-p25). Three patients (with overlapping triplicated segment 2p23-p25) had diaphragmatic hernia. Abnormal rotation of the heart or L-transposition of large vessels (with or without visceral heterotaxia) was found in two infants (overlapping triplicated segment 2p23-p24). In two patients with common triplicated segment 2p22.3-p25, neuroblastoma has been described. The occurrence of all these defects may be explained either by the action of the same gene(s) mapped to 2p24 or by action of some independent factors located in different segments of the short arm. Although the latter hypothesis is much less probable, it can not be rejected at the present time. We propose the existence of a genetic system controlling surveillance of an abnormal embryo to explain the phenotypic differences between patients with the same imbalance within a family. In some "restrictive" combinations the abnormal embryos will die, although in "permissive" combinations they can survive.
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PMID:Trisomy 2p: analysis of unusual phenotypic findings. 771 24

Although pediatric solid tumors are cytogenetically less well characterized than childhood leukemias, an understanding of the role of chromosomal changes in the development of these neoplasms is emerging. The major clinical importance of chromosome analysis today is diagnostic. Especially in small cell round cell tumors of childhood, the unique karyotypic patterns that characterize some of the differential diagnostic entities make it possible to determine with a high degree of certainty which type of cancer the child has. Molecular studies have revealed that almost all retinoblastomas show homozygous loss of function of the RB1 gene in 13q14. At the cytogenetic level, however, aberrations of 13q are seen in less than 25% of retinoblastomas; instead, the presumably progression-related i(6p) and aberrations leading to gain of 1q predominate, each being present in one-third of the tumors. Twenty percent of cytogenetically aberrant Wilms' tumors show structural rearrangements, often deletions, of 11p13 and 11p15, where the WT1 and WT2 genes map. Other frequent changes are trisomy 12 and duplication of 1q. The most common (80%) cytogenetic abnormality in neuroblastoma is loss of distal 1p, a chromosome segment thought to harbor at least two tumor-suppressor genes of importance in tumorigenesis. Double minute chromosomes or homogeneously staining regions are present in one-third of all neuroblastomas and are associated with MYCN amplification. Loss of 1p material or MYCN amplification predicts a poor outcome. The most common (30%) chromosomal aberration in primitive neuroectodermal tumors of the central nervous system is i(17q). The formation of this isochromosome may help inactivate a tumor-suppressor gene located distal to the TP53 locus on 17p. No specific chromosome abnormality has been detected in gliomas, but monosomy 22 and rearrangements leading to loss of 1p and gain of 1q are recurrent. Few hepatoblastomas with chromosomal changes have been reported, but several potential primary aberrations have been described, including +2, +20, and duplication 8q. In Ewing's sarcoma, t(11;22)(q24;q12) is the primary aberration, with trisomy 8 and gain of 1q being frequent secondary changes. Fibrosarcomas in children often carry only numeric aberrations, especially trisomy for chromosomes 11, 20, 17, and 8. Most osteosarcomas are cytogenetically complex, and no specific abnormality has been detected; the single most common change is loss of chromosome 13, which is observed in half the tumors. In contrast, the low-malignancy parosteal osteosarcomas often display supernumerary ring chromosomes as the sole karyotypic deviation. The cytogenetic profiles of rhabdomyosarcomas differ among the various morphologic subtypes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytogenetic analysis in the examination of solid tumors in children. 794 9

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

Familial neuroblastoma occurs rarely. We studied a family with three children; one of them has a disseminated (stage 4) and another has a localized (stage 2) neuroblastoma. We observed subtelomeric locus D1Z2 (1p36) deletion in both tumors by using double-color fluorescence in situ hybridization. The MYNC gene was found in single copy in both tumors. Loss of heterozygosity (LOH) and restriction fragment length polymorphism analyses were performed by using DNA from frozen tumor cells and from microdissected tumor areas excised from paraffin-embedded sections. We detected somatic LOH at locus D1S468 (1p36) in a tumor-cell population with a trisomy 1 of the stage-2 patient. Neuroblastoma cells of the stage-4 patient were diploid and showed allelic loss at the following loci: D1S172, D1S80, D1S94, D1S243, D1S468, D1S214, D1S241, and D1S164. Haplotype study showed that the siblings inherited the same paternal 1p36-->pter chromosome region by homologous recombination and that, in the two tumors, arm 1p of different chromosomes of maternal origin was damaged. Our results suggest that the siblings inherited the predisposition to neuroblastoma associated with paternal 1p36 region and that tumors developed as a consequence of somatic loss of the maternal 1p36 allele.
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PMID:Neuroblastoma in two siblings supports the role of 1p36 deletion in tumor development. 1008 45

Neuroblastoma is the commonest extracranial solid tumour in children. There are a number of molecular genetic features known which are of prognostic importance and which are used to direct therapy. Identification and targeting of high-risk individuals with intensive therapeutic regimens may allow an improvement in survival rates. The most powerful biological parameters associated with prognosis in this malignancy are chromosomal changes, especially MYCN amplification, deletion of chromosome 1p and aneuploidy. Rapid characterization of these aberrations at the time of diagnosis is paramount if stratification according to risk group is to be achieved. This paper describes the rapid detection of del(1p), MYCN amplification and trisomy using interphase fluorescence in situ hybridization on imprints from fresh tumour biopsies. The results are related to those obtained by standard molecular methods and karyotyping.
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PMID:Fluorescence in situ hybridization techniques for the rapid detection of genetic prognostic factors in neuroblastoma. United Kingdom Children's Cancer Study Group. 1088 66


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