MDM2 gene amplification in bone and soft‐tissue tumors: Association with tumor progression in differentiated adipose‐tissue tumors

Nakayama, Tomitaka; Toguchida, Junya; Wadayama, Bun‐Ichiro ‐I; Kanoe, Hiroshi; Kotoura, Yoshihiko; Sasaki, Masao S.

doi:10.1002/ijc.2910640511

Cited by 120 publications

(86 citation statements)

References 13 publications

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“…For example, Oliner et al, (1992) reported ampli®cation of MDM2 in 3/11 (27%) cases of OSA; however, others have identi®ed MDM2 ampli®cation in only 4 ± 7% of cases (Nakayama et al, 1995;Miller et al, 1996;Lonardo et al, 1997). We found SAS ampli®ed in 6/6 parosteal OSA and 2/16 intramedullary tumors.…”

Section: Discussionmentioning

confidence: 45%

Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas

et al. 1999

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Ampli®cation of genes in the 12q13-15 region occurs frequently in several malignancies including osteosarcoma. The products of these ampli®ed genes are thought to provide cancer cells with a selective growth advantage; however, the speci®c gene(s) driving this amplicon is unknown. We have previously shown that the SAS gene is ampli®ed in most parosteal osteosarcomas. In this study we analysed additional putative growth regulatory genes in this chromosomal region in 24 primary osteosarcoma specimens. CDK4 and SAS were coampli®ed in 6/6 parosteal tumors, and MDM2 was also ampli®ed in 4/5 parosteal cases. In comparison, ampli®cation occurred in only 2/16 classical intramedullary osteosarcomas and involved the SAS gene. Each ampli®ed gene had a correspondingly elevated mRNA level. Four high grade intramedullary tumors had elevated mRNA expression of SAS, but did not exhibit gene ampli®cation. Gene ampli®cation/overexpression was not associated with metastatic disease and did not change markedly with tumor progression, as evidenced by analysis of sequential tumor specimens from eight patients. Three other genes in the 12q13-15 region (CDK2, WNT1 and WNT10b) were not ampli®ed in any of the tumors. The di erent patterns of gene ampli®ca-tion and overexpression of CDK4, SAS and MDM2 in parosteal and intramedullary osteosarcomas may help explain the disparity in the biological behaviour of these two types of osteosarcoma.

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Section: Discussionmentioning

confidence: 45%

Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas

et al. 1999

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“…20,25,26,29,37 Scoring as positive only those normal and neoplastic lesions, such as in uterine cases showing at least 3-fold amplification (MDM2 smooth muscle tumors and as a prognostic indicator copy number ú 6), very similar figures were reported in malignancies, such as soft tissue tumors 45 and by Nakayama et al (4.5%; n Å 67) 25 and Miller et al…”

Section: Discussionmentioning

confidence: 71%

“…27 Amplification of MDM2 has been associated with recurrent or metastasic OS in some studies, 26 but not in others. 25 …”

mentioning

confidence: 99%

p53 and MDM2 alterations in osteosarcomas

Lonardo¹,

Ueda²,

Huvos³

et al. 1997

Cancer

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by quantitative Southern blot analysis and immunohistochemistry, respectively. M utations in the p53 gene are the most common alteration found in human malignant tumors. 1,2 Its crucial role in the control of cell growth has been demonstrated both in vivo 3-5 and in vitro. 6,7 p53 has further been implicated in mediating programmed cell death, 8 including apoptosis induced by radiation and chemotherapeutic agents. 9,10 The inhibitory role of p53 in cell growth has been linked to its ability to stimulate transcription of the cycle-dependent kinase (CDK) inhibitor p21. 11 Several lines of evidence suggest a role for p53 in the pathogenesis of osteosarcoma (OS) in particular. Alterations of p53 have frequently been found in uncultured tissue samples of OS with a frequency ranging from 18 -42%. [12][13][14][15][16] OS is known to occur The MDM2 gene, which codes for a protein with the ability to Medical Center for Cancer, Osaka, Japan.bind both p53 18 and retinoblastoma protein (Rb) 19 and to inhibit the bors the gene for CDK4. 27 Amplification of MDM2 has been associated with recurrent or metastasic OS in some studies, 26 but not in others. 25

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“…It has been reported that over 50% of osteosarcomas have a LOH at the Rb locus, and a higher probability of metastasis has been observed in patients with loss of pRb (Wadayama et al, 1994;Benassi et al, 1999). The event-free survival rate at 60 months is 100% for patients without LOH, 43% for all patients with Rb LOH and 65% for non-metastatic patients with Rb LOH (Feugeas et al, 1996).…”

Section: Sarcomasmentioning

confidence: 99%