Genetic heterogeneity and clonal evolution in neuroblastoma

Tumour heterogeneity and clonal evolution at the genetic level may explain the development of malignant or resistant disease during clinical progressi on of neuroblastoma (NB). In this report we use 1 p allelic analysis and DN A ploidy to evaluate clonal heterogeneity and clonal selection in vivo. We studied a total of 69 tumours from 29 patients with NB. To evaluate turnour heterogeneity and clonal evolution in vivo we used a panel of polymorphic allelic markers mapping to chromosome 1. 33 tumours from 12 patients (group 1) were obtained from different sites during the same surgery or at sequen tial surgeries without intervening chemotherapy to evaluate genetic heterog eneity. Paired samples from 10 patients (group 2) were used to evaluate clo nal selection before and after chemotherapy. In 6 cases paired tumours and derived cell lines were studied. Analysis of DNA ploidy changes by karyotyp e, FISH and flow cytometry was performed in 15 tumours from 6 multiply recu rred local-regional (LR) NB patients. Allelotype study revealed that 66% (8 /12) of group 1 samples were heterogeneous, with distinct allelic patterns in turnour samples separated by time or location. In group 2 allelic patter ns were different in post-chemotherapy specimens in 60% (6/10). DNA ploidy analysis showed that pre-chemotherapy samples contained 2 distinct ploidy c lones, one diploid and one triploid, whereas all post-chemotherapy tumor sa mples were 100% diploid. These findings suggest that NB exhibits a high deg ree of clonal heterogeneity and clonal evolution occurs during the course o f therapy and clinical progression. (C) 2001 Cancer Research Campaign hftp: //www.bjcancer.com.