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 neurobl astoma (NB). We performed loss of heterozygosity (LOH) analysis of 120 well characterized NB to better define specific regions of 1p loss and any asso ciation with clinical and biological prognostic features (DNA index, MYCN, age, and stage). All categories of disease were represented including 7 gan glioneuromas, 8 stage 4S, 33 local-regional (stages 1, 2, and 3), and 72 st age 4 NB according to the International Neuroblastoma Staging System. Patie nts were consistently treated with stage-appropriate protocols at a single institution. Sixteen highly informative, polymorphic loci mapping to chromo some 1 were evaluated using a sensitive, semi-automated, fluorescent detect ion system. Chromosome arm 1p deletions were detected in all categories of tumor except ganglioneuroma. Frequent LOH was detected at two separate regi ons of 1p and distinct patterns of losses were associated with individual c linical/biological categories. Clinically aggressive stage 4 tumors were pr edominantly diploid with extensive LOH frequently detected in the region of 1pte1 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 reg ions of loss primarily involving terminal regions of 1p36 (42%). Most spont aneously regressing stage 4S tumors (7/8) were hyperdiploid without loss of 1p36 or 1p22. These findings suggest that genes located on at least two se parate 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/bio logical categories.