54111

HNB1

-;hereditary neuroblastoma 1;HNB1;hereditary neuroblastoma 1

-

16p13-p12

unknown

Hereditary predisposition to develop neuroblastoma (Online Mendelian Inheritancein Man 256700), a pediatric cancer of the sympathetic nervous system, segregatesas an autosomal dominant Mendelian trait. We performed linkage analysis on sevenfamilies with two or more first-degree relatives affected with neuroblastoma to localize a hereditary neuroblastoma predisposition gene. A single interval at chromosome bands 16p12-13 was the only genomic region consistent with linkage (LOD(MAX) = 3.30 at D16S764). Identification of informative recombination eventsin linked families defined a 28.0-cM region between D16S748 and D16S769 that cosegregated with the disease in each pedigree. Loss of heterozygosity was identified in 5 of 11 familial neuroblastomas and 68 of 336 nonfamilial neuroblastomas (20.2%) at multiple 16p polymorphic loci. A 14.5-cM smallest region of overlap of somatic deletions was identified within the interval defined by linkage analysis (tel-D16S500-D16S412-cen). Taken together, these data suggest that a hereditary neuroblastoma predisposition gene (HNB1) is located at 16p12-13 and that disruption of this gene may contribute to the pathogenesis of nonfamilial neuroblastomas.

This is a comprehensive overview on the most recent developments in diagnosis and treatment of acute lymphoblastic leukemia (ALL). Dr. Dieter Hoelzer and colleagues give an overview of current chemotherapy approaches, prognostic factors, risk stratification, and new treatment options such as tyrosine kinase inhibitors and monoclonal antibodies. Furthermore the role of minimal residual disease (MRD) for individual treatment decisions in prospective clinical studiesin adult ALL is reviewed. Drs. Ching-Hon Pui and Mary Relling discuss late treatment sequelae in childhood ALL. The relation between the risk of second cancer and treatment schedule, pharmacogenetics, and gene expression profile studies is described. Also pathogenesis, risk factors, and management of other complications such as endocrinopathy, bone demineralization, obesity, and avascular necrosis of bone is reviewed. Dr. Fred Appelbaum addresses long-term results, late sequelae and quality of life in ALL patients after stem cell transplantation. New options for reduction of relapse risk, e.g., by intensifiedconditioning regimens or donor lymphocyte infusions, for reduction of mortality and new approaches such as nonmyeloablative transplantation in ALL are discussed. Drs. Jacques van Dongen and Tomasz Szczepanski demonstrate the prognostic value of MRD detection via flow cytometry or PCR analysis in childhood ALL. They discuss the relation between MRD results and type of treatment protocol, timing of the follow-up samples, and the applied technique and underline the importanceof standardization and quality control. They also review MRD-based risk group definition and clinical consequences.