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p53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines
Medical and pediatric oncology, 2000-08, Vol.35 (2), p.96-103
Taylor, Alan C.
Shu, Lili
Danks, Mary K.
Poquette, Catherine A.
Shetty, Sheetal
Thayer, Mathew J.
Houghton, Peter J.
Harris, Linda C.
2000
Details
Autor(en) / Beteiligte
Taylor, Alan C.
Shu, Lili
Danks, Mary K.
Poquette, Catherine A.
Shetty, Sheetal
Thayer, Mathew J.
Houghton, Peter J.
Harris, Linda C.
Titel
p53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines
Ist Teil von
Medical and pediatric oncology, 2000-08, Vol.35 (2), p.96-103
Ort / Verlag
New York: John Wiley & Sons, Inc
Erscheinungsjahr
2000
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Background The p53 tumor suppressor gene is the most commonly mutated gene in human cancer, and mutations arise in a wide variety of tumor types. Wild‐type p53 functions as a regulator of apoptosis, so mutations in the p53 gene are generally associated with aggressive tumors and a poor prognosis. Procedure We have investigated the p53 mutation and MDM2 amplification frequencies in biopsies from pediatric rhabdomyosarcoma (RMS) tumors and cell lines by SSCP and Southern analyses. Results A mutation was detected in only 1 of 20 tumor specimens (5%), whereas the frequency in established RMS cell lines was significantly higher (6/10, 60%). p53 Mutations were more common in cell lines derived from tumors previously exposed to chemotherapy compared to those derived from tumors at di‐agnosis, and it is likely that these mutations enhanced the probability of successful long‐term culture. The frequency of MDM2 gene amplification in patient biopsies was also low (2/20, 10%). Interestingly, complete responses to treatment were obtained in the two patients with tumors that demonstrated amplification of MDM2. The response to treatment of patients with tumors wild‐type for p53 and without MDM2 amplification was quite varied, indicating that expression of a wild‐type p53 gene at diagnosis cannot always facilitate a favorable outcome. Conclusions p53 mutation and MDM2 gene amplification frequencies are extremely low in RMS tumors, but a wild‐type p53 genotype is not always associated with a favorable prognosis. Med. Pediatr. Oncol. 35:96–103, 2000. © 2000 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0098-1532
eISSN: 1096-911X
DOI: 10.1002/1096-911X(200008)35:2<96::AID-MPO2>3.0.CO;2-Z
Titel-ID: cdi_proquest_miscellaneous_71249726
Format
–
Schlagworte
Adolescent
,
Adult
,
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
,
Biological and medical sciences
,
Blotting, Southern
,
Cell Line
,
chemotherapy
,
Child
,
Child, Preschool
,
Combined Modality Therapy
,
Diseases of the osteoarticular system
,
Exons
,
Gene Amplification
,
Humans
,
Infant
,
MDM2
,
Medical sciences
,
Mutation
,
Neoplasm Proteins - genetics
,
Nuclear Proteins
,
p53
,
Polymorphism, Single-Stranded Conformational
,
Prognosis
,
Proto-Oncogene Proteins - genetics
,
Proto-Oncogene Proteins c-mdm2
,
rhabdomyosarcoma
,
Rhabdomyosarcoma - drug therapy
,
Rhabdomyosarcoma - genetics
,
Rhabdomyosarcoma - pathology
,
SSCP analysis
,
Tumor Suppressor Protein p53 - genetics
,
Tumors of striated muscle and skeleton
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