Myc oncogene activation in B and T lymphoid tumours

1985 ◽  
Vol 226 (1242) ◽  
pp. 59-72 ◽  
Keyword(s):  
Chromosome 15 ◽  
Chromosome 6 ◽  
Coding Region ◽  
Chromosome Translocations ◽  
Myc Oncogene ◽  
Chain Locus ◽  
Oncogene Activation ◽  
Selection For ◽  
T Lymphomas ◽  
B Lymphoid

The chromosome translocations characteristic of certain B lymphoid tumours associate the myc oncogene and immunoglobulin loci. The typical t(12;15) in murine plasmacytomas and analogous t(14;8) in Burkitt lyphomas couple the myc coding region to one of the switch recombination regions within the immunoglobulin heavy (H) chain locus; hence the switch machinery may promote some translocations. Significantly, translocation induces constitutive myc expression, the untranslocated myc allele remaining silent. The predilection for breakpoints near the 5´ end of the c -myc gene may reflect selection for altered myc regulation. In most tumours, the stimulatory effect of the H locus context is not understood, but an H locus enhancer participates in some tumours, including one displaying a novel transposition . The variant (6;15) translocations found in about 15 % of plasmacytomas involve the myc band and the region of chromosome 6 where the k locus lies. The t(6;15) is shown here to represent an exchange between C K and a chromosome 15 locus (designated pvt -1) which lies unexpectedly far from c-myc .The association of myc expression with pvt -1 alterations suggest that myc can be activated at a distance. Myc has also been implicated in some T lymphomas by detection of proviral inserts near myc and also surprisingly, within the pvt -1 locus. Inserts near myc appear to activate its expression via the retroviral enhancer.

scholarly journals A complex translocation at the murine kappa light-chain locus.

1987 ◽  
Vol 7 (11) ◽  
pp. 4130-4133 ◽  
Author(s):  
M A Shapiro ◽  
M Weigert
Keyword(s):  
Light Chain ◽  
Chromosome 12 ◽  
Chromosome 15 ◽  
Chromosome 6 ◽  
Kappa Light Chain ◽  
Complex Translocation ◽  
Immunoglobulin Kappa ◽  
Complex Series ◽  
Chain Locus ◽  
Light Chain Locus

We have previously reported that a segment of DNA from a murine plasmacytoma comprises DNA from three chromosomes, the immunoglobulin kappa light-chain locus on chromosome 6, the S mu locus on chromosome 12, and a region on chromosome 15. We now report that the reciprocal product contains DNA from only the kappa locus and chromosome 15 and not from S mu. We conclude that a complex series of events, including both a transposition of DNA and a translocation between chromosomes, generated these imperfect reciprocal products.

A complex translocation at the murine kappa light-chain locus

1987 ◽  
Vol 7 (11) ◽  
pp. 4130-4133
Author(s):  
M A Shapiro ◽  
M Weigert
Keyword(s):  
Light Chain ◽  
Chromosome 12 ◽  
Chromosome 15 ◽  
Chromosome 6 ◽  
Kappa Light Chain ◽  
Complex Translocation ◽  
Immunoglobulin Kappa ◽  
Complex Series ◽  
Chain Locus ◽  
Light Chain Locus

We have previously reported that a segment of DNA from a murine plasmacytoma comprises DNA from three chromosomes, the immunoglobulin kappa light-chain locus on chromosome 6, the S mu locus on chromosome 12, and a region on chromosome 15. We now report that the reciprocal product contains DNA from only the kappa locus and chromosome 15 and not from S mu. We conclude that a complex series of events, including both a transposition of DNA and a translocation between chromosomes, generated these imperfect reciprocal products.

Proviral integration site Mis-1 in rat thymomas corresponds to the pvt-1 translocation breakpoint in murine plasmacytomas

1986 ◽  
Vol 6 (5) ◽  
pp. 1834-1837
Author(s):  
L Villeneuve ◽  
E Rassart ◽  
P Jolicoeur ◽  
M Graham ◽  
J M Adams
Keyword(s):  
B Lymphocyte ◽  
Integration Site ◽  
Translocation Breakpoint ◽  
Chromosome 15 ◽  
Proviral Integration ◽  
Murine Chromosome ◽  
Proviral Integration Site ◽  
Murine Homolog ◽  
T Lymphomas

Two loci independently implicated in T-and B-lymphocyte neoplasia are shown to be equivalent. The Mis-1 locus is a common proviral integration site in retrovirally induced rat T lymphomas, while the pvt-1 locus on murine chromosome 15 frequently translocates to the kappa locus in plasmacytomas bearing 6;15 translocations. By comparing cloned sequences, we show that pvt-1 is the murine homolog of Mis-1.

Mouse c-myc oncogene is located on chromosome 15 and translocated to chromosome 12 in plasmacytomas

Science ◽  
1982 ◽  
Vol 218 (4579) ◽  
pp. 1319-1321 ◽  
Author(s):  
S Crews ◽  
R Barth ◽  
L Hood ◽  
J Prehn ◽  
K Calame
Keyword(s):  
Chromosome 12 ◽  
Chromosome 15 ◽  
Myc Oncogene

Chromosomal location of the regulator of mouse alpha-fetoprotein, Afr-1.

Genetics ◽  
1988 ◽  
Vol 119 (3) ◽  
pp. 687-691
Author(s):  
E P Blankenhorn ◽  
R Duncan ◽  
K Huppi ◽  
M Potter
Keyword(s):  
Mouse Chromosome ◽  
Chromosomal Location ◽  
Serum Levels ◽  
Alpha Fetoprotein ◽  
Chromosome 15 ◽  
Myc Oncogene ◽  
Close Proximity ◽  
B Mice

Abstract Afr-1 is a gene whose product contributes to the adult regulation of mouse alpha-fetoprotein (AFP). In Afr-1b/b homozygotes, the adult serum levels of AFP are 10- to 20-fold higher than in Afr-1a/a or Afr-1a/b mice. The studies reported here were performed to map the Afr-1 gene. Our results show that Afr-1 resides on mouse chromosome 15, approximately 25 cM from Gdc-1. Afr-1 appears to be located in close proximity to the mouse c-myc oncogene. These results are discussed with respect to the susceptibility or resistance of different BALB/c sublines (which are either Afr-1a or Afr-1b, respectively) to pristane-induced plasmacytomas.

scholarly journals Expression of the c-myc oncogene under control of an immunoglobulin enhancer in E mu-myc transgenic mice.

1987 ◽  
Vol 7 (4) ◽  
pp. 1436-1444 ◽  
Author(s):  
W S Alexander ◽  
J W Schrader ◽  
J M Adams
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
B Lymphocyte ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Myc Oncogene ◽  
Feedback Model ◽  
B Lymphocyte Development ◽  
B Lymphoid ◽  
Spleen And Lymph Nodes

Transgenic mice bearing a cellular myc oncogene coupled to the immunoglobulin heavy-chain enhancer (E mu) exhibit perturbed B-lymphocyte development and succumb to B lymphoid tumors. To investigate how the enhancer has affected myc expression, we analyzed the structure and abundance of myc transcripts in tissues of prelymphomatous mice and in the lymphomas. Expression of the E mu-myc transgene appeared to be confined largely to B lymphoid cells, being dominant in bone marrow, spleen, and lymph nodes, with no detectable expression in T cells or other hematopoietic lineages examined. The myc transcripts initiated very predominantly at the normal myc promoters, although use of the more upstream myc promoter was accentuated and an enhancer-associated promoter may be used infrequently. The level of E mu-myc transcripts in the preneoplastic lymphoid tissues and in the E mu-myc tumors was not markedly higher than myc RNA levels in proliferating normal lymphocytes. Thus, enforced expression of structurally normal myc transcripts at only a modestly elevated level has profound biological consequences. The absence of detectable endogenous c-myc RNA in any tumor, or in preneoplastic bone marrow, supports a negative feedback model for normal c-myc regulation.

scholarly journals Frequent c-myc oncogene activation and infrequent presence of Epstein- Barr virus genome in AIDS-associated lymphoma

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 667-671
Author(s):  
M Subar ◽  
A Neri ◽  
G Inghirami ◽  
DM Knowles ◽  
R Dalla-Favera
Keyword(s):  
Epstein Barr Virus ◽  
Virus Genome ◽  
Gene Rearrangements ◽  
High Grade ◽  
Histologic Type ◽  
Myc Oncogene ◽  
Barr Virus ◽  
Oncogene Activation ◽  
Myc Gene ◽  
Epstein Barr

Sixteen cases of histologic intermediate-grade and high-grade AIDS- associated non-Hodgkin's lymphoma (NHL) were studied for the presence and patterns of c-myc gene and bcl-2 locus rearrangements. The presence of Epstein-Barr virus (EBV) sequences and proteins and HTLV-I sequences were also investigated. c-myc gene rearrangements analogous to those observed in sporadic Burkitt lymphomas were detected in 12 of 16 cases. Six of 16 cases had detectable EBV sequences and proteins. None of the cases displayed bcl-2 rearrangements or contained HTLV-I sequences. These data suggest a frequent role for c-myc activation in the pathogenesis of AIDS-associated NHL, independent of histologic type. Conversely, EBV does not appear to be directly involved in lymphomagenesis in the majority of AIDS-associated NHLs.

Modes of c-myc Oncogene Activation in Murine Plasmacytomas

1984 ◽  
pp. 146-153 ◽  
Author(s):  
J. Q. Yang ◽  
J. F. Mushinski ◽  
L. W. Stanton ◽  
P. D. Fahrlander ◽  
P. C. Tesser ◽  
...  
Keyword(s):  
Myc Oncogene ◽  
Oncogene Activation

Deregulation of the c-myc oncogene in virus-induced thymic lymphomas of AKR/J mice

1986 ◽  
Vol 6 (11) ◽  
pp. 4088-4092
Author(s):  
A Reicin ◽  
J Q Yang ◽  
K B Marcu ◽  
E Fleissner ◽  
C F Koehne ◽  
...  
Keyword(s):  
High Frequency ◽  
Blot Hybridization ◽  
Proximal Promoter ◽  
S1 Nuclease ◽  
Myc Oncogene ◽  
Strong Shift ◽  
Oncogene Activation ◽  
Mink Cell ◽  
Promoter Usage ◽  
Distal Promoter

A high frequency (greater than or equal to 65%) of thymomas induced by mink cell focus-forming virus 69L1 in AKR/J mice contain proviral integrations which are clustered 0.7-kilobase upstream of the c-myc oncogene predominantly in the opposite transcriptional orientation. Blot hybridization experiments showed that on the average there was only a twofold elevation of steady-state c-myc RNA in the thymomas as compared with levels in normal AKR/J thymocytes. Such an increase would not appear to be sufficient as a mechanism of oncogene activation in this system. In contrast, S1 nuclease analysis of transcripts initiated from the two known c-myc promoters indicated a strong shift in promoter usage in virtually all thymomas tested. In normal thymus the ratio of transcripts initiated from the proximal promoter P1 to the distal promoter P2 was 0.2 to 0.3. In contrast, most of the thymomas tested (18 of 23) showed an average P1/P2 ratio of 1.2 regardless of whether or not proviral integrations could be detected within a 21-kilobase EcoRI fragment containing the three c-myc exons. We conclude that alterations in P1/P2 ratios are good indicators of c-myc deregulation in thymic lymphomas.

Mechanism of endogenous myc gene down-regulation in E mu-N-myc tumors

1991 ◽  
Vol 11 (1) ◽  
pp. 440-444
Author(s):  
A Ma ◽  
R K Smith ◽  
A Tesfaye ◽  
P Achacoso ◽  
R Dildrop ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Leukemia Virus ◽  
Transcriptional Level ◽  
Down Regulation ◽  
Myc Oncogene ◽  
Myc Gene ◽  
B Lymphoid ◽  
High Level ◽  
Transformed Cell Lines

Transgenic mouse lines carrying the N-myc oncogene deregulated by the immunoglobulin heavy-chain enhancer spontaneously develop B-lymphoid tumors (R. Dildrop, A. Ma, K. Zimmerman, E. Hsu, A. Tesfaye, R. DePinho, and F. W. Alt, EMBO J. 8:1121-1128, 1989; H. Rosenbaum, E. Webb, J. M. Adams, S. Cory, and A. W. Harris, EMBO J. 8:749-755). Permanent cell lines derived from these tumors (E mu-N-myc cell lines) express extremely high levels of the N-myc transgene but little or no detectable endogenous N-myc or c-myc. We have employed nuclear run-on assays to show that down-regulation of endogenous N- and c-myc expression occurs at the transcriptional level. To determine whether the lack of endogenous myc gene transcription is a direct effect of high-level N-myc transgene expression, we have generated Abelson murine leukemia virus (A-MuLV)-transformed cell lines from prelymphomatous E mu-N-myc mice (A-MuLV/E mu-N-myc cell lines). Although these A-MuLV/E mu-N-myc lines express very high levels of the N-myc transgene, they continue to transcribe the endogenous c-myc gene. These findings demonstrate that high-level N-myc gene expression alone does not necessarily lead to down-regulation of endogenous myc gene expression and suggest that events associated with transformation by N-myc may be critical to this process.

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