Expression of multiple drug resistance gene, MDR1, and N-myc oncogene in an Italian population of human neuroblastoma patients.
Thirty-four patients of an Italian population affected by neuroblastoma (NB) were evaluated at diagnosis for multidrug resistance gene (MDR1) and N-myc oncogene amplification. No patients showed MDR1 amplification, while extra copies of the N-myc gene were found in 9 out of 34 patients (26%). N-myc amplification was correlated (p = 0.008) with a shorter progression-free survival. RNA was purified from fresh tumor biopsies and analysed in 29 NB samples. MDR1 gene expression was found to be increased in 5 out of 29 tumor samples at onset (17%) and in 1 out of 3 at relapse, but none of them expressed both MDR1 and N-myc genes simultaneously. No correlation was found between MDR1 or N-myc genes expression and tumor progression. MDR1 mRNA transcription may occur spontaneously after onset, suggesting that certain NB tumors could be resistant to antineoplastic drugs at onset. All 5 patients showing MDR1 mRNA transcription achieved complete or partial clinical remission after polychemotherapy. This was presumably due to inclusion in the therapeutic protocol of a high dose of Cisplatin, a drug not susceptible to the effects of the MDR1 gene product. Our findings show that cells which actively transcribe for the MDR1 gene are present in several untreated NB patients. No gene amplification was detected and probably the MDR1 gene expression is regulated at the transcriptional level.
Corrias
M V
MV
Pediatric Oncology Research Laboratory, G. Gaslini Children's Hospital, Genova, Italy.
Cornaglia-Ferraris
P
P
Di Martino
D
D
Stenger
A M
AM
Lanino
E
E
Boni
L
L
Tonini
G P
GP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004351:Drug Resistance / Q000235:genetics*; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger