Clinical categories of neuroblastoma are associated with different patterns of loss of heterozygosity on chromosome arm 1p.
Deletion of the short arm of chromosome 1 is frequently observed in neuroblastoma (NB). We performed loss of heterozygosity (LOH) analysis of 120 well characterized NB to better define specific regions of 1p loss and any association with clinical and biological prognostic features (DNA index, MYCN, age, and stage). All categories of disease were represented including 7 ganglioneuromas, 8 stage 4S, 33 local-regional (stages 1, 2, and 3), and 72 stage 4 NB according to the International Neuroblastoma Staging System. Patients were consistently treated with stage-appropriate protocols at a single institution. Sixteen highly informative, polymorphic loci mapping to chromosome 1 were evaluated using a sensitive, semi-automated, fluorescent detection system. Chromosome arm 1p deletions were detected in all categories of tumor except ganglioneuroma. Frequent LOH was detected at two separate regions of 1p and distinct patterns of losses were associated with individual clinical/biological categories. Clinically aggressive stage 4 tumors were predominantly diploid with extensive LOH frequently detected in the region of 1ptel to 1p35 (55%) and at 1p22 (56%). The shortest region of overlap for LOH at 1p36 was between D1S548 and D1S1592 and for 1p22 was between D1S1618 and D1S2766. Local-regional tumors were mostly hyperdiploid with short regions of loss primarily involving terminal regions of 1p36 (42%). Most spontaneously regressing stage 4S tumors (7/8) were hyperdiploid without loss of 1p36 or 1p22. These findings suggest that genes located on at least two separate regions of chromosome arm 1p play a significant role in the biology of NB and that distinct patterns of 1p LOH occur in individual clinical/biological categories.
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J
J
Mora
N K
NK
Cheung
B H
BH
Kushner
M P
MP
LaQuaglia
K
K
Kramer
M
M
Fazzari
G
G
Heller
L
L
Chen
W L
WL
Gerald
D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*
D014408:Biomarkers, Tumor