Frequent loss of heterozygosity on chromosomes 4, 12 and 19 in radiation-induced lymphomas in mice

Okumoto, Masaaki; Park, Yeong-Gwan; Song, Chuyi; Mori, Nobuko

doi:10.1016/s0304-3835(98)00305-x

Cited by 23 publications

(23 citation statements)

References 14 publications

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supporting

confidence: 76%

“…2), suggesting that this chromosome was probably completely deleted. P6 cells retained three SSLP markers located on proximal chromosome 4 but had lost two others which map to the central and distal regions ( was also observed in studies of Mo-MLV-and radiation-induced thymomas (8,25,30,32).…”

Section: Fig 1 Loss Of Chromosome 4 Proviruses Dnas From Cxcb Cellsupporting

confidence: 57%

“…For example, a fraction of Moloney murine leukemia virus (Mo-MLV)-induced thymomas (25) and mammary tumors arising in mouse mammary tumor virus transgenic mice (9) have lost sequences on several chromosomes. Similar changes have also been noted in radiation-induced hematopoietic tumors in mice (8,30,32,47).The large number of endogenous nonecotropic proviruses carried by inbred mice provide polymorphic markers that facilitate such an analysis (15, 49). Most inbred mice carry between 30 and 60 of these proviruses, and their chromosomal locations have been mapped in many inbred mouse strains (15).…”

mentioning

confidence: 66%

“…A number of other mouse tumors, including hepatocellular carcinomas (29), lung carcinomas (18), insulinomas (11), and chemically induced thymomas (63), also show similar low frequencies of allelic loss at different chromosomal sites. However, radiation-induced lymphomas display much higher frequencies of allelic loss (8,30,32,47), suggesting that both the tumor type and the way in which the tumor is induced affect LOH.…”

Section: Discussionmentioning

confidence: 99%

“…Chromosome 4 has been identified as a target of LOH in several murine lymphoma models (8,25,30,32). However, because the deletions are very large in all these cases, implicating a particular gene has not been possible.…”

Section: Discussionmentioning

confidence: 99%

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Loss of Heterozygosity at theInk4a/ArfLocus Facilitates Abelson Virus Transformation of Pre-B Cells

Mostecki¹,

Halgren²,

Radfar

et al. 2000

J Virol

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In many tumor systems, analysis of cells for loss of heterozygosity (LOH) has helped to clarify the role of tumor suppressor genes in oncogenesis. Two important tumor suppressor genes, p53 and the Ink4a/Arf locus, play central roles in the multistep process of Abelson murine leukemia virus (Ab-MLV) transformation. p53 and the p53 regulatory protein, p19Arf, are required for the apoptotic crisis that characterizes the progression of primary transformed pre-B cells to fully malignant cell lines. To search for other tumor suppressor genes which may be involved in the Ab-MLV transformation process, we used endogenous proviral markers and simple-sequence length polymorphism analysis to screen Abelson virus-transformed pre-B cells for evidence of LOH. Our survey reinforces the role of the p53-p19 regulatory pathway in transformation; 6 of 58 cell lines tested had lost sequences on mouse chromosome 4, including the Ink4a/Arf locus. Consistent with this pattern, a high frequency of primary pre-B-cell transformants derived from Ink4a/Arf ؉/؊ mice became established cell lines. In addition, half of them retained the single copy of the locus when the transformation process was complete. These data demonstrate that a single copy of the Ink4a/Arf locus is not sufficient to fully mediate the effects of these genes on transformation.Abelson murine leukemia virus (Ab-MLV) is a rapidly transforming retrovirus that can induce lymphomas in vivo and transform pre-B cells and immortalized fibroblast cell lines in vitro (reviewed in references 39 and 40). The virus carries the v-abl oncogene, and the protein tyrosine kinase it encodes is required for transformation. Despite the strong growth-stimulatory signal provided by the v-Abl protein, Ab-MLV-induced transformation is a multistep process both in vivo and in vitro (16,17,59,60), suggesting that multiple cellular changes are required before a cell becomes fully malignant. Analysis of primary pre-B-cell transformants in vitro has revealed that the p53 tumor suppressor gene and the p19Arf gene, the product of which regulates p53 function (reviewed in references 35 and 46), are intimately involved in the process by which these cells evolve to become fully malignant established cell lines (37,52,54). About 50% of all transformants contain mutations affecting p53 (52), and many others express very low levels of the p19Arf protein, a molecule that stabilizes p53, thereby enhancing its function (37).The factors involved in tumor progression in the Ab-MLV system have received limited attention, and most studies using Ab-MLV or other oncogenic retroviruses have focused on oncogene cooperativity (reviewed in reference 42). However, in many other types of tumors, dominant growth-stimulatory signals generated by oncogenes cooperate with the loss of growthsuppressive signals provided by tumor suppressor genes (26,45). Alterations in the p53 and NF1 tumor suppressor genes have been reported in some retrovirus-induced tumors (3-6, 53, 56, 61). Other studies have identified chromosomal regions ...

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supporting

confidence: 76%

Section: Fig 1 Loss Of Chromosome 4 Proviruses Dnas From Cxcb Cellsupporting

confidence: 57%

mentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Loss of Heterozygosity at theInk4a/ArfLocus Facilitates Abelson Virus Transformation of Pre-B Cells

Mostecki¹,

Halgren²,

Radfar

et al. 2000

J Virol

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Cutaneous T‐cell lymphoma in a 21‐year‐old male with Wolf–Hirschhorn syndrome

Batton¹,

Amanullah²,

Main³

et al. 2003

American J of Med Genetics Pt A

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We describe a case of cutaneous T-cell lymphoma occurring in a 21-year-old male with Wolf-Hirschhorn syndrome (WHS) due to a chromosome 4p16.3 deletion. This is the first documented case report of malignancy occurring in an adult with WHS. We also review the literature regarding patients with WHS and the joint occurrence of malignancy and discuss genetic changes involving chromosome 4 which may have contributed to the genesis of our patient's lymphoma.

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Two cases of hepatic adenomas in patients with wolf‐hirschhorn syndrome: A new rare complication?

Prunotto

Cianci

Cereda

et al. 2013

American J of Med Genetics Pt A

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Wolf-Hirschhorn syndrome (WHS) is a rare microdeletion syndrome associated with a characteristic facial appearance, failure to thrive, psychomotor delays, and various major malformations of internal organs; many medical complications have been described (feeding difficulties, epilepsy, hearing problems). Benign or malignant oncologic problems are not a typical feature of the natural history of these patients. We report on two patients with WHS patients in whom hepatic adenoma (HA) were diagnosed during adolescence. The clinical evolution of liver involvement was different between the two. We discuss the possibility of considering HA as a rare medical problem in the follow-up of WHS patients. © 2013 Wiley Periodicals, Inc.

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Frequent loss of heterozygosity on chromosomes 4, 12 and 19 in radiation-induced lymphomas in mice

Cited by 23 publications

References 14 publications

Loss of Heterozygosity at theInk4a/ArfLocus Facilitates Abelson Virus Transformation of Pre-B Cells

Loss of Heterozygosity at theInk4a/ArfLocus Facilitates Abelson Virus Transformation of Pre-B Cells

Cutaneous T‐cell lymphoma in a 21‐year‐old male with Wolf–Hirschhorn syndrome

Two cases of hepatic adenomas in patients with wolf‐hirschhorn syndrome: A new rare complication?

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