Cytogenetic findings and prognosis in neuroblastoma with emphasis on marker chromosome 1

Abstract

The relationship between cytogenetic findings and prognosis in 51 pediatric patients with neuroblastoma is described. Patients were classified into the following four groups based on karyotypic findings: (1) near diploidy, 42 to 47 chromosomes (n = 11); (2) hyperdiploidy, 50 to 56 chromosomes (n = 4); (3) near triploidy, 60 to 77 chromosomes (n = 33); and (4) hypotetraploidy, 80 to 83 chromosomes (n = 3). Patients with near diploid or hypotetraploid karyotypes also had several structural abnormalities including marker chromosome 1, with or without double minutes (DM) or homogeneously staining regions (HSR). Most of these patients were 1 year of age or older and had advanced tumors. The patients who were in the hyperdiploid or near triploid category had few structural abnormalities; all of them, except one, were younger than 1 year of age, had localized tumors, and are long-term, disease-free survivors. Kaplan-Meier analysis of survival rates disclosed a significant difference favoring the latter group (P < 0.001).

Genomic structure and mutational analysis of the human KIF1B gene which is homozygously deleted in neuroblastoma at chromosome 1p36.2

“…Cytogenetic studies have suggested that deletion of the short arm of chromosome 1 (1p) occurs frequently in NB (Brodeur and Fong, 1981;Hayashi et al, 1989), and is associated with a poor prognosis (Hayasi et al, 1989;Brodeur et al, 1989;Caron et al, 1996). Molecular genetic studies have revealed several speci®c alterations in NB.…”

“…Molecular genetic studies have revealed several speci®c alterations in NB. One of these is ampli®cation of the MYCN gene that is associated with a poor prognosis in NB (Seeger et al, 1985;Hayashi et al, 1989;Brodeur and Fong, 1989). Another is the loss of heterozygosity (LOH) at the 1p (Fong et al, , 1992Takita et al, 1995;Schwab et al, 1996), long arm of chromosome 11 (11q) (Srivatsan et al, 1993) and 14q (Srivatsan et al, 1993;Suzuki et al, 1989) in NB.…”

Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenografts

“…At diagnosis, nearly 50% of neuroblastomas are metastatic, mainly to the bone marrow. Several biological tumour parameters such as N-myc gene amplification (Brodeur et al, 1984), loss of heterozygosity of chromosome lp (Fong et al, 1989;Hayashi et al, 1989), diploidy (Hayashi et al, 1989) and mdrl gene overexpression (Bourhis et al, 1989;Chan et al, 1991) have been identified as strong predictors of a poor outcome. Despite the use of intensive chemotherapy protocols, including high-dose chemotherapy followed by autologous bone marrow stem cell support, the survival of children treated for non-metastatic neuroblastoma with Nmyc amplification or for metastatic neuroblastoma (over 1 year of age) remains poor.…”

Biology of tumors of the peripheral nervous system

“…Both N-myc amplification (Brodeur, 1990a;Brodeur et al, 1984;Bourhis et al, 1991;Seeger et al, 1985) and deletion of chromosome lp (as detected by cytogenetic analysis) (Christiansen and Lampert, 1988;Hayashi et al, 1989;Kaneko et al, 1987) appear strongly correlated with a poor clinical outcome and with each other, but it is not yet clear if they are independent prognostic variables. Nevertheless, they appear to characterize a genetically distinct subset of very aggressive neuroblastomas.…”