Allele‐specific loss or imbalance of chromosomes 9, 15, and 16 in B‐cell tumors from interspecific F1 hybrid mice carrying eμ‐c‐
            <i>myc</i>
            or N‐
            <i>myc</i>
            transgenes

Linardopoulos, Spiros; Silva, Santiago; Klein, George; Balmain, Allan

doi:10.1002/1097-0215(20001215)88:6<920::aid-ijc13>3.0.co;2-#

Cited by 8 publications

(3 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, in a previous study of chromosomal rearrangements in murine lymphomas, although allelic imbalance of chromosome 15 markers was detected frequently, no trisomy 15 was found in E-c-myc lymphomas (0/7), in contrast to non-transgenic controls (7/19). 42 This suggests that amplification of c-myc may be involved in the selection of trisomy 15 in the EBNA-1.26 tumors and provides further evidence that EBNA-1 and c-myc are not redundant in their oncogenic action and act cooperatively instead.…”

Section: Karyotypic Analyses Of Tumor Samplesmentioning

confidence: 80%

“…The numbers are few, however, this may reflect selection of an amplified c-myc locus in the EEBNA-1 tumors, which would not be selected for in mice bearing the E-c-myc transgene. 42 If this is the case, it would support the hypothesis that EBNA-1 and myc act cooperatively.…”

Section: Transposon Tagging In Eebna-1 Mice Using Momlvmentioning

confidence: 85%

“…The most common chromosomal abnormality identified in the EμEBNA‐1 transgenic lymphomas was trisomy 15 (that bears the c‐myc locus), whereas no trisomy 15 was evident in the lymphomas from EBNA‐1/c‐myc bitransgenic mice. The numbers are few, however, this may reflect selection of an amplified c‐myc locus in the EμEBNA‐1 tumors, which would not be selected for in mice bearing the Eμ‐c‐myc transgene 42. If this is the case, it would support the hypothesis that EBNA‐1 and myc act cooperatively.…”

Section: Discussionmentioning

confidence: 98%

See 2 more Smart Citations

Epstein‐Barr virus nuclear antigen‐1 and Myc cooperate in lymphomagenesis

Drotar

Silva

Barone

et al. 2003

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

The lymphomagenic action of myc genes in conjunction with Epstein-Barr virus nuclear antigen-1 (EBNA-1) have been examined using transgenic mice in several separate tests. Synergy between Myc and EBNA-1 in lymphomagenesis was revealed in a cross breed study where co-expression of transgenic myc and EBNA-1 led to a tumor latency period reduced significantly in some crosses. In the resulting bitransgenic tumors, expression of the E-myc genes was not af- The virus was discovered in cell cultures from endemic Burkitt's lymphoma (BL) samples 2 and has since been found to have a very high association (Ͼ95%) with this disease. The more rare, sporadic form of BL (occurring worldwide) shows 15-25% association with EBV. Similarly, only a proportion (30 -40%) of the AIDS form of BL is positive for EBV genomes. Nevertheless, in all EBV-associated cases, the viral episomal genome is thought to be clonal, indicating that the virus was present in the tumor progenitor cell. This would argue that the probability of evolving into a tumor is higher for an EBV carrying than an EBV negative B-lymphocyte suggesting that the virus is causal in the genesis of the tumor. 3 Notably, all BL tumors carry a reciprocal chromosomal translocation between chromosome 8, in the proximity of the c-myc gene and one of chromosomes 14, 2, or 22 at the immunoglobulin heavy (IgH) or light (IgL) chain loci. This leads to deregulation of c-myc expression. 4 -6 Several transgenic mouse models to examine myc induced tumorigenesis have been developed. Overexpression of c-myc or N-myc in B cells using the IgH (E) intronic enhancer predisposes transgenic mice to B cell lymphoma. [7][8][9][10][11][12][13] The exact pathology of the c-myc induced tumors and the timing of onset varies according to the precise transgene construct used. Using an IgL locus enhancer instead to drive c-myc overexpression slightly later in B cell development results in a transgenic lymphoma with a pathology startlingly similar to BL. 14 In EBV-associated BL tumors a restricted subset of the viral latent genes is expressed. Of 6 EBV nuclear antigens (EBNA), EBNA-1 is the only one that has been detected consistently. 15,16 In addition the 2 small, polymerase III, untranslated RNAs (EBER-1 and -2) are expressed. LMP2A transcripts and the BamHI-A rightward transcripts have also been detected in BL biopsies. 17 EBV is a potent B cell transforming virus, nevertheless the role it plays in the genesis of BL remains unclear. The theory that EBV continues to contribute to the malignant phenotype of established tumor cells is suggested by the stable retention of the viral genome in cultured BL cell lines and by the loss of tumorigenicity of sub clones of BL cell lines that have lost the viral genome. 18,19 In this manner, the EBERs have been shown to contribute to the transformed phenotype in Akata cells, 20 and EBER expression can substitute for the presence of viral genomes in EBV positive Akata and Mutu I cell lines. This was not the case, however, for all the BL cell lines examined, suggest...

show abstract

Section: Karyotypic Analyses Of Tumor Samplesmentioning

confidence: 80%

Section: Transposon Tagging In Eebna-1 Mice Using Momlvmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Epstein‐Barr virus nuclear antigen‐1 and Myc cooperate in lymphomagenesis

Drotar

Silva

Barone

et al. 2003

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

Search for unknown tumor‐antagonizing genes

Imreh

Klein

Zabarovsky

2003

Genes Chromosomes & Cancer

Self Cite

View full text Add to dashboard Cite

Following the ingenious prediction of Alfred Knudson in 1971, the first tumor suppressor gene, RB1, has been isolated. Its product, the RB1 protein, was found to play a major role in the control of the cell cycle. The loss of heterozygosity (LOH) technique, introduced by Cavenee and colleagues, was an important milestone toward the confirmation of Knudson's hypothesis and the identification of the gene. Subsequently, the LOH technique has provided important clues that have led to the discovery of other tumor suppressor genes. Most of them play important roles in the regulation of the cell cycle and/or of apoptosis. Circumstantial evidence suggests that still other and perhaps many unknown genes may participate in the protection of the organism against malignant growth. The numerous genome losses in tumors, detected by LOH, comparative genomic hybridization, and by cytogenetic techniques, support this possibility. The early work of one of us (G.K.), together with Henry Harris and Francis Wiener, had shown that the malignant phenotype can be suppressed by hybridizing malignant with low- or non-tumorigenic cells. However, analysis of this phenomenon failed to assign the inhibition of tumorigenicity to any particular gene. We have pursued the search for new tumor-antagonizing genes with two unconventional approaches, focusing on human chromosomal subband 3p21.3, a region frequently targeted by cytogenetically detectable deletions. We have detected four clusters of candidate tumor suppressor genes at 3p21.3 by a combination of deletion mapping and the "elimination test." These findings raise the question whether the number and variety of genes that may contribute to the defense against uncontrolled proliferation may have been underestimated.

show abstract

Comparative human/murine sequence analysis of the common eliminated region 1 from human 3p21.3

et al. 2002

View full text Add to dashboard Cite

Interspecies sequence comparison offers an effective approach to identify conserved elements that might have functional importance. We compared 1.32 Mb of C3CER1 (referred also as CER1) from human Chromosome (Chr) 3p21.3 to its orthologous regions on mouse Chr 9F. The corresponding mouse region was found divided into two blocks, but their gene content and gene positions were highly conserved between human and mouse. We observed that two orthologous mouse genes (Xtrp3s1 and Cmkbr1) were duplicated, and this resulted in two additional expressed mouse genes (Xtrp3 and Cmkbr111). We also recognized a large number of conserved elements that were neither exons, CpG islands, nor repeats. We further identified and characterized five novel orthologous mouse genes (Kiaa0028, Xtrp3s1, Fyco1, Tmem7, and Lrrc2).

show abstract

Allele‐specific loss or imbalance of chromosomes 9, 15, and 16 in B‐cell tumors from interspecific F1 hybrid mice carrying eμ‐c‐ myc or N‐ myc transgenes

Cited by 8 publications

References 24 publications

Epstein‐Barr virus nuclear antigen‐1 and Myc cooperate in lymphomagenesis

Epstein‐Barr virus nuclear antigen‐1 and Myc cooperate in lymphomagenesis

Search for unknown tumor‐antagonizing genes

Comparative human/murine sequence analysis of the common eliminated region 1 from human 3p21.3

Contact Info

Product

Resources

About