Chromosome 1p and 11q deletions and outcome in neuroblastoma.
BACKGROUND
Neuroblastoma is a childhood cancer with considerable morbidity and mortality. Tumor-derived biomarkers may improve risk stratification.


METHODS
We screened 915 samples of neuroblastoma for loss of heterozygosity (LOH) at chromosome bands 1p36 and 11q23. Additional analyses identified a subgroup of cases of 11q23 LOH with unbalanced 11q LOH (unb11q LOH; defined as loss of 11q with retention of 11p). The associations of LOH with relapse and survival were determined.


RESULTS
LOH at 1p36 was identified in 209 of 898 tumors (23 percent) and LOH at 11q23 in 307 of 913 (34 percent). Unb11q LOH was found in 151 of 307 tumors with 11q23 LOH (17 percent of the total cohort). There was a strong association of 1p36 LOH, 11q23 LOH, and unb11q LOH with most high-risk disease features (P<0.001). LOH at 1p36 was associated with amplification of the MYCN oncogene (P<0.001), but 11q23 LOH and unb11q LOH were not (P<0.001 and P=0.002, respectively). Cases with unb11q LOH were associated with three-year event-free and overall survival rates (+/-SE) of 50+/-5 percent and 66+/-5 percent, respectively, as compared with 74+/-2 percent and 83+/-2 percent among cases without unb11q LOH (P<0.001 for both comparisons). In a multivariate model, unb11q LOH was independently associated with decreased event-free survival (P=0.009) in the entire cohort, and both 1p36 LOH and unb11q LOH were independently associated with decreased progression-free survival in the subgroup of patients with features of low-risk and intermediate-risk disease (P=0.002 and P=0.02, respectively).


CONCLUSIONS
Unb11q LOH and 1p36 LOH are independently associated with a worse outcome in patients with neuroblastoma.
Attiyeh
Edward F
EF
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, PA 19104-4318, USA.
London
Wendy B
WB
Mossé
Yael P
YP
Wang
Qun
Q
Winter
Cynthia
C
Khazi
Deepa
D
McGrady
Patrick W
PW
Seeger
Robert C
RC
Look
A Thomas
AT
Shimada
Hiroyuki
H
Brodeur
Garrett M
GM
Cohn
Susan L
SL
Matthay
Katherine K
KK
Maris
John M
JM
D000704:Analysis of Variance; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D005784:Gene Amplification; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
D005819:Genetic Markers; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins