Chromosomes that show partial loss or gain in near-diploid tumors coincide with chromosomes that show whole loss or gain in near-triploid tumors: evidence suggesting the involvement of the same genes in the tumorigenesis of high- and low-risk neuroblastomas.
We performed two-color fluorescence in situ hybridization analysis to detect the numbers of chromosomes 1 and 17, 1p deletion, and 17q gain in 177 neuroblastomas, including 101 tumors that were found by a mass-screening program for infants. Sixty-eight tumors with disomy 1 or tetrasomy 1 were classified as the Dis1 group, and 109 tumors with trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells with tetrasomy 1 were classified as the Tris1 group. 17q gain was the most frequent genetic event, followed by 1p deletion, and MYCN amplification in both Dis1 and Tris1 tumors. However, the incidence of all the genetic events was higher in Dis1 tumors than in Tris1 tumors. These findings suggest that Tris1 tumors are more resistant to acquiring the genetic events than are Dis1 tumors. In addition, there was an accumulation of genetic events in more advanced stages, with the exception of a high incidence of 17q gain in the stage IVS Tris1 tumors. Comparative genomic hybridization analysis, which was performed in 59 of the 177 tumors, showed that chromosomes partially lost or gained in Dis1 tumors coincided with chromosomes totally lost or gained in Tris1 tumors. Dis1 and Tris1 tumors were considered to have near-diploid/tetraploid and near-triploid/pentaploid chromosome numbers, respectively. These findings suggest that the same tumor-suppressor genes or oncogenes may be involved in the development and progression of both high- and low-risk neuroblastomas, and that the ploidy state of the tumor plays a fundamental role in the heterogeneous behavior.
Tomioka
Nobumoto
N
Departments of Cancer Chemotherapy and Medicine, Saitama Cancer Center Hospital, Saitama, Japan.
Kobayashi
Hirofumi
H
Kageyama
Hajime
H
Ohira
Miki
M
Nakamura
Yohko
Y
Sasaki
Fumiaki
F
Todo
Satoru
S
Nakagawara
Akira
A
Kaneko
Yasuhiko
Y
D022981:Allelic Imbalance / Q000235:genetics; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D020732:Cytogenetic Analysis / Q000379:methods; D004171:Diploidy; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015999:Multivariate Analysis; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging / Q000379:methods; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization; D015513:Oncogene Proteins / Q000235:genetics; D011123:Polyploidy; D016019:Survival Analysis
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins