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. Copyright 2000 Wiley-Liss, Inc.
BACKGROUND: The p53tumor suppressor gene is the most commonly mutated gene in humancancer, 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. Copyright 2000 Wiley-Liss, Inc.
Authors: Aishwarya G Jacob; Dennis O'Brien; Ravi K Singh; Daniel F Comiskey; Robert M Littleton; Fuad Mohammad; Jordan T Gladman; Maria C Widmann; Selvi C Jeyaraj; Cheryl Bolinger; James R Anderson; Donald A Barkauskas; Kathleen Boris-Lawrie; Dawn S Chandler Journal: Neoplasia Date: 2013-09 Impact factor: 5.715
Authors: Jack F Shern; Li Chen; Juliann Chmielecki; Jun S Wei; Rajesh Patidar; Mara Rosenberg; Lauren Ambrogio; Daniel Auclair; Jianjun Wang; Young K Song; Catherine Tolman; Laura Hurd; Hongling Liao; Shile Zhang; Dominik Bogen; Andrew S Brohl; Sivasish Sindiri; Daniel Catchpoole; Thomas Badgett; Gad Getz; Jaume Mora; James R Anderson; Stephen X Skapek; Frederic G Barr; Matthew Meyerson; Douglas S Hawkins; Javed Khan Journal: Cancer Discov Date: 2014-01-23 Impact factor: 39.397