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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The MOLT-16 cell line, which was established from the malignant cells of a patient with T-cell acute lymphoblastic leukemia, is characterized by a translocation involving chromosome 8 (band q24) and chromosome 14 (band q11) [t(8;14)(q24;q11)]. To determine the position of the gene encoding the alpha chain of the T-cell receptor and of the protooncogene MYC (formerly c-myc) in relation to the breakpoint junction and to evaluate their possible role in the pathogenesis of T-cell neoplasia, we applied the techniques of in situ chromosomal hybridization, Southern blot analysis, and molecular cloning to MOLT-16 cells. Our results indicate that the breakpoint on chromosome 14 at band q11 occurs close to a joining sequence of the gene encoding the alpha chain of the T-cell receptor. The constant region and part of the joining region of this gene are translocated to the 3' side of the MYC exons. The breakpoints on chromosomes 8 and 14 are close to, but distinct from, those found in SKW-3, another T-cell leukemia cell line, which has a t(8;14). The identification of a breakpoint to the 3' side of MYC suggests that this recurring translocation is analogous to the variant t(2;8) and t(8;22) translocations observed in the B-cell malignancies.
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PMID:Molecular cloning of the breakpoint junction of a human chromosomal 8;14 translocation involving the T-cell receptor alpha-chain gene and sequences on the 3' side of MYC. 352 89

The c-myc nuclear associated oncoprotein has been quantitated simultaneously with DNA in nuclei extracted from archival biopsies of uterine cervix neoplasia. The oncoprotein and DNA were measured fluorimetrically in a flow cytometer using a mouse monoclonal antibody (MYC 1-6E10) and propidium iodide. Normal biopsies exhibited higher oncoprotein levels than carcinomas (P less than 0.00001). Furthermore, the maximum fluorescence signal in the normal tissue occurred at a lower antibody concentration compared with tumour tissue. There was no correlation between oncoprotein levels and histological grade, stage of disease, age of the patients or prognosis in the carcinomas. Aneuploidy, defined as a distinct second peak separate from the diploid distribution, was not a significant feature. The c-myc oncoprotein nuclear content does not appear to be a prognostic indicator in carcinoma of the cervix from the results of these studies but there is clearly diagnostic potential, particularly for automated analysis of cervical screening.
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PMID:Flow cytometric quantitation of DNA and c-myc oncoprotein in archival biopsies of uterine cervix neoplasia. 355 16

The transcription of human nm23 genes (nm23-H1, nm23-H2) is involved in suppression of tumor metastasis or tumor progression. Therefore the characterization of transcriptional regulatory mechanisms for both nm23 genes is very important. In this study we have isolated and analyzed the 5'-flanking region of the human nm23-H2 gene and estimated the distance to 4 kb between nm23-H2 and nm23-H1 genes. We localized the known microsatellite D17S396 within this region. Furthermore the identification of possible binding sites for MYC proteins and additionally the NM23-H2 protein itself (the transcription factor PuF for c-myc gene activation) is of importance with respect to possible para- and autoregulatory interactions. A comparison of the promoter sequences of both human nm23 genes revealed no significant sequence homology.
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PMID:Characterization of the human nm23-H2 promoter region and localization of the microsatellite D17S396. 748 60

A case of acute myeloid leukemia (M-3) with complex karyotypic aberrations and double minute (dmin) chromosomes is presented. The patient had no history of prior exposure to mutagenic or carcinogenic agents or of other malignancies. She died from CNS involvement six weeks after the initial diagnosis. We used comparative genomic hybridization to identify the amplified sequences presumed to represent the dmin of the leukemic cells; the tumor/normal ratios indicated increased signal intensity at 8q24. This localization prompted investigation by semi-quantitative PCR that revealed amplification of the MYC oncogene. The extent of chromosome aberrations and the oncogene amplification, both linked with poor prognosis, may relate to the rapid course of this patient's disease.
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PMID:Extrachromosomal gene amplification in acute myeloid leukemia; characterization by metaphase analysis, comparative genomic hybridization, and semi-quantitative PCR. 750 27

About half of the patients with follicular lymphoma will develop an aggressive B cell lymphoma with morphological changes in growth pattern and cellular morphology. Changes of the immunophenotype, especially of the expression of immunoglobulin (Ig) have been documented less frequently. Multiple tumor samples of two patients with follicular lymphoma who developed tumor progression, were studied by Southern blot analysis for rearrangements of the Ig genes and the oncogenes BCL2 and MYC. In both patients, the general pattern of Ig gene rearrangements, especially of the Ig light-chain genes, and the structure of the t(14;18) breakpoint as assessed by the polymerase chain reaction (PRC) and fine restriction mapping, remained unaltered with time. However, both within the functional Ig heavy-chain allele and around the t(14;18) breakpoint, extensive secondary alterations took place. This indicates clonal evolution rather than the appearance of an independent lymphoma. In the first case with progression from follicular lymphoma to Burkitt's lymphoma 3 years after diagnosis, alterations were especially present 3' of the t(14;18) breakpoint. In the second patient with a change from follicular to diffuse centroblastic lymphoma 4 years after diagnosis, subsequent class switches from IgM to IgG and to defective IgH expression were accompanied by deletion of C mu sequences and a rearrangement of the MYC gene, respectively. Additionally, in both patients alterations in individual restriction sites occurred, which most likely were due to somatic mutations within both the functional IgH and translocated allele. Our data indicate that complex alterations of both the functional and non-functional IgH allele may accompany tumor progression and may erroneously suggest the appearance of independent clones by Southern blot analysis. It remains to be established whether these alterations are causative events or the consequence of genetic instability and clonal evolution.
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PMID:Histological conversion of follicular lymphoma with structural alterations of t(14;18) and immunoglobin genes. 756 20

The AKT2 gene is one of the human homologues of v-akt, the transduced oncogene of the AKT8 virus, which induces lymphomas in mice. In previous studies, AKT2, which codes for a serine-threonine protein kinase, was shown to be amplified and overexpressed in some human ovarian carcinoma cell lines and amplified in primary tumors of the ovary. To confirm and extend these findings, we conducted a large-scale, multicenter study of AKT2 alterations in ovarian and breast cancer. Southern-blot analysis demonstrated AKT2 amplification in 16 of 132 (12.1%) ovarian carcinomas and in 3 of 106 (2.8%) breast carcinomas. No AKT2 alteration was detected in 24 benign or borderline tumors. Northern-blot analysis revealed overexpression of AKT2 in 3 of 25 fresh ovarian carcinomas which were negative for AKT2 amplification. The difference in the incidence of AKT2 alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis. No significant association was found between AKT2 amplification and amplification of the proto-oncogenes MYC and ERBB2, suggesting that amplification of AKT2 defines an independent subset of breast and ovarian cancers. Ovarian cancer patients with AKT2 alterations appear to have a poor prognosis. Amplification of AKT2 was especially frequent in undifferentiated tumors (4 of 8, p = 0.019), suggesting that AKT2 alterations may be associated with tumor aggressiveness.
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PMID:Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. 765 93

The product of the retinoblastoma gene (RB1) is believed to function as a negative regulator of cell growth. Recent experimental results suggest that RB1 may exert its growth-suppressing activity by regulating the transcription of a variety of growth-related genes, including FOS, MYC, and TGFBI. A series of biochemical and molecular analyses suggest that RB1 indirectly affects gene expression via cell-cycle-regulated interactions with transcription factors, such as E2F and SPI. Determination of the mechanisms regulating such protein-protein interactions and the identification of additional targets of RB1 function will provide vital insights into the role of this tumor-suppressor gene in mammalian cell proliferation.
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PMID:Regulation of transcription by the retinoblastoma protein. 768 Aug 89

Cytogenetically visible gene amplification structures can consist of arrays of amplicons presumably formed by secondary "rearrangements" following amplicon formation. The structural evolution of gene amplification sites in tumor cells suggests that complex secondary structures may have some selective advantage in the tumor cell environment. Although secondary amplicon rearrangements are a hallmark of the gene amplification process, little is known about the mechanics of this process. COLO320 neuroendocrine tumor cells carry two different types of amplified MYC oncogene sequences, one type with an intact MYC gene and the other with a rearranged "chimeric" MYC gene. We have studied various clonal subpopulations of COLO320 cells and identified regions within and downstream of the MYC locus that are unique to each amplicon type. Using double-label fluorescence in situ hybridization with DNA probes unique to each amplicon type, we have observed that both chromosomal and extrachromosomal MYC amplicon arrays in COLO320 cells frequently consist of heterogeneous mixtures of each MYC amplicon type. Our results suggest that the two MYC amplicon types of COLO320 cells were formed simultaneously but independently, and that double minute chromosomes observed in COLO320 cells were formed by intermolecular homologous recombination secondary to amplicon formation.
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PMID:Recombination between separate MYC amplification structures in COLO320 cells. 768 5

We previously proposed that a local duplication, not the loss of the subsequently amplified marker from its original site, might be the first step in gene amplification in human cells. It is important to investigate this issue in naturally occurring amplification and when copy numbers are relatively low. We have examined the location of single-copy and amplified 11q13 sequences in cell lines from human breast cancers and squamous cell carcinomas using fluorescence in situ hybridization both with a probe specific for the 11q13 amplifying region and with a chromosome 11-specific library. We show that in most cell lines the 11q13 amplicons are physically linked to chromosome 11 or to a chromosome derived from chromosome 11 by various rearrangements near the 11q13 region. In none of the cell lines were interstitial deletions of 11q13 detected. These results indicate that 11q13 amplification in human tumor cells generally does not involve deletion as the initial step. One cell line with chromosomally located amplified 11q13 sequences contained double minutes that harbored the MYC gene but no 11q13 sequences. This suggests that the genetic outcome and the mechanism of gene amplification are probably dependent on specific DNA sequences rather than on the origin of the cells.
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PMID:Amplification of the 11q13 region in human carcinoma cell lines: a mechanistic view. 768 56

Quantitative imbalance in chromosomal material relative to the normal diploid situation is the most conspicuous genetic change in breast tumors, affecting virtually all chromosomes in varying frequencies. This imbalance is reflected by deviant DNA stemlines observed in DNA flow cytometry analysis, by numerical chromosome abnormalities in karyotype analysis and by loss of heterozygosity in DNA polymorphism studies. Gene amplification might be caused by the same genetic mechanisms that cause these chromosomal abnormalities [134]. The number of known genes for which there is now good evidence for their role in the development of breast cancer is still limited, and basically restricted to TP53 and ERBB2. Clearly, the estrogen receptor, not discussed here, can be conjectured to be of importance in breast cancer development, yet the significance of the reported sequence variants [157] for hormone-independent growth is presently undetermined [158]. For many others, such as MYC, CCND1, EMS1, EGF, RB1, NME, DCC and prohibitin, the evidence is still largely circumstantial, or obtained only by in vitro studies on breast cancer cell lines. In many cases of chromosomal imbalance and certainly those affecting whole chromosomes or chromosome arms, it is unclear what their effect on tumor growth will be, because multiple potential candidate genes are located in the affected region. In addition, it is obvious that multiple chromosomes are affected simultaneously in a single tumor, but that the total set of chromosome changes varies in different tumors. This intra- and intertumor heterogeneity of chromosome involvement suggests that an unknown number of the observed abnormalities are not important for tumor development, but merely result from genetic instability. On the other hand, there is accumulating evidence, particularly from flow cytometry and allelotype studies reviewed here, to suggest that the genetic evolution associated with tumor development and progression does reach a stage of equilibrium despite the presence of extensive tumor heterogeneity. The number of genetic events found per tumor raises the question whether each event of heterozygosity loss represents the second step in the inactivation of a tumor suppressor gene. Also, LOH observed with polymorphic markers can sometimes be interpreted as allelic copy number gain instead of loss. Possibly, some of these allelic imbalances contribute to the tumorigenic process simply because they create a dosage effect in certain gene products [2]. This supposes that the sole presence of allelic imbalance at certain chromosomes is sufficient to provide selective growth advantage in certain cases.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Somatic genetic changes in human breast cancer. 781 70


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