"Retroposon" insertion into the cellular oncogene c-myc in canine transmissible venereal tumor.

Katzir, Nurit; Rechavi, Gideon; Cohen, Justus B.; Unger, Tamar; Simoni, Frida Brok; Segal, Shraga; Cohen, Dan; Givol, David

doi:10.1073/pnas.82.4.1054

Cited by 112 publications

(66 citation statements)

References 42 publications

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“…Pathogenic insertions of both non-autonomous and autonomous elements have been characterized (Kazazian, 1998) like an Alu insertion in human neurofibromatosis (Wallace et al, 1991) or an ETn insertion in murine myotonia (Steinmeyer et al, 1991). Similarly, LINE-1 insertion has been reported to suppress the expression of clotting factor VIII in a case of haemophilia (Kazazian et al, 1988) or of the dystrophin gene in Duchenne's muscular dystrophy (Holmes et al, 1994), to activate c-myc in tumours (Katzir et al, 1985;Morse et al, 1988), and to disrupt the APC gene in colorectal cancer (Miki et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

et al. 2002

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LINE-1 are endogenous mobile genetic elements that have dispersed and accumulated in the genomes of eukaryotes via germline transposition, with up to 100 000 copies in mammalian genomes. LINE-1 elements transpose by reverse transcription of their own transcript. Transposition requires synthesis of a full-length, sense-strand transcripts and proteins encoded by open reading frame (ORF) 1 and ORF2. Although severely repressed in most normal tissues, LINE-1 occasionally leads to disease by insertional mutagenesis. In the present study, Northern blot and in situ hybridization analyses revealed a template-strand transcription of LINE-1 ORF2 (encoding reverse transcriptase, RT) in lymphoid organs and the liver from MRL-+/+ and Fas-deficient MRL/lpr strains and their normal ancestors. While these sense transcripts are restricted to the nucleus in hepatocytes, they are also found in the cytoplasm in splenocytes. In contrast to transcription, ORF2 translation was detected only in MRL strains, as shown by the cytoplasmic labelling of splenic cells obtained with a monoclonal antibody recognizing the LINE-1 RT. This antibody coprecipitated two proteins of 45 and 12 kDa from MRL/lpr lymphoid organ lysates that were removed by pretreatment with anti-b2-microglobulin antiserum, suggesting a structural association between a LINE-1 product and a major histocompatibility complex class I or class I-like molecule.

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Section: Discussionmentioning

confidence: 99%

Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

et al. 2002

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“…Further evidence for clonal transmission of CTVT was provided by the identification of a LINE element insertion near the MYC locus in the CTVT genome (Table 1; Katzir et al, 1985). This genomic rearrangement has been identified in a large set of globally distributed CTVT tumors, but not in any other canine tissue, and is now considered diagnostic evidence for CTVT (Katzir et al, 1987;Amariglio et al, 1991;Choi et al, 1999;Chu et al, 2001b;Choi and Kim, 2002;Liao et al, 2003b;Murgia et al, 2006;Park et al, 2006;Vazquez-Mota et al, 2008;Rebbeck et al, 2009).…”

Section: Ctvtmentioning

confidence: 99%

Clonally transmissible cancers in dogs and Tasmanian devils

2008

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Tasmanian devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT) are the only known naturally occurring clonally transmissible cancers. These cancers are transmitted by the physical transfer of viable tumor cells that can be transplanted across histocompatibility barriers into unrelated hosts. Despite their common etiology, DFTD and CTVT have evolved independently and have unique life histories and host adaptations. DFTD is a recently emerged aggressive facial tumor that is threatening the Tasmanian devil with extinction. CTVT is a sexually transmitted tumor of dogs that has a worldwide distribution and that probably arose thousands of years ago. By contrasting the biology, molecular genetics and immunology of these two unusual cancers, I highlight the common and unique features of clonally transmissible cancers, and discuss the implications of clonally transmissible cancers for host-pathogen evolution.

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“…Primers P1 and T3 were designed to cover 1.6 kb of the LINE-c-myc insertion, 20 between the 5Ј end of c-myc, outside the first exon, and the 3Ј end of the LINE gene. 9 Another set of primers, Myc S-2 and LINE AS1, was designed to cover a 553-bp segment extending from the 5Ј end of the first c-myc exon of the LINE insertion ( Fig.…”

Section: Primersmentioning

confidence: 99%

Identification of Canine Transmissible Venereal Tumor Cells Using in Situ Polymerase Chain Reaction and the Stable Sequence of the Long Interspersed Nuclear Element

et al. 2003

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Abstract. Canine transmissible venereal tumor (CTVT) is a unique tumor that can be transplanted across the major histocompatibility complex (MHC) barrier by viable tumor cells. In dogs, CTVT grows progressively for a few months and then usually regresses spontaneously. A long interspersed nuclear element (LINE) insertion is found specifically and constantly in the 5Ј end of the CTVT cell c-myc gene, outside the first exon. The rearranged LINE-c-myc gene sequence has been used with polymerase chain reaction (PCR) to diagnose CTVT. However, in CTVT cells, the total length of the inserted LINE gene is not constant. In this experiment, variation in the inserted LINE gene was studied to determine which parts of the LINE sequence can be used as primers to identify CTVT cells with in situ PCR (IS PCR). The LINE gene was inserted between the TATA boxes in the promoter region of c-myc. In CTVT cells, deletions of different lengths are frequent in this gene. However, the 550-bp segment at the 5Ј end of the LINE-c-myc gene was stable. Thus, primers were designed to cover the stable 0.55-kb segment from the 5Ј end outside the first exon of the c-myc gene to the 5Ј end of LINE gene stable segment. With these primers and IS PCR, individual CTVT cells in formalin-fixed tissue sections and CTVT cultures were identified. Cells from other canine tumors were negative for this gene. In addition, the CTVT-specific, 0.55-kb segment was not found in any spindle-shaped cells from progressive or regressive phase CTVT. The IS PCR technique also did not detect any positive spindle-shaped cells in CTVT cell cultures. Thus, fibroblastic terminal differentiation is less likely to be a mechanism for spontaneous regression of CTVT cells.Canine transmissible venereal tumor (CTVT) is a naturally occurring tumor transmitted by viable tumor cells. CTVT cells are small and round, with a large nucleolus and prominent cytoplasm in which cytoplasmic vacuolization is common. Although the origin of CTVT cells has not been well defined, studies using immunohistochemical staining indicate that the tumor origin is histiocytic. 25,27 The normal chromosome number for dogs is 78, and only the sex chromosomes are metacentric. In CTVT cells, the number of chromosomes ranges from 57 to 59, and 16 to 18 chromosomes are metacentric. 28,31 Transposable elements (TE), or transposons, are a group of discrete genes that transport themselves directly from one site to another within the genome. 26 Transposon activity has been associated with chromosomal rearrangements, such as deletions, duplications, inversions, and translocations, and the recombination of host genomes. A 1.6-kb-long interspersed nuclear element (LINE), 20 a TE sequence or retroposon, was found in CTVT cells, inserted in the 5Ј end of the c-myc gene, outside the first exon. The truncated LINE-1 element has been sequenced, 7 and it contains a 1,378-bp insert flanked by a 10-bp direct repeat upstream of the c-myc gene. The DNA sequence of the

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"Retroposon" insertion into the cellular oncogene c-myc in canine transmissible venereal tumor.

Cited by 112 publications

References 42 publications

Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

Clonally transmissible cancers in dogs and Tasmanian devils

Identification of Canine Transmissible Venereal Tumor Cells Using in Situ Polymerase Chain Reaction and the Stable Sequence of the Long Interspersed Nuclear Element

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