1q23 gain is associated with progressive neuroblastoma resistant to aggressive treatment

Abstract

Neuroblastoma is one of the most common malignant tumors of childhood and is characterized by regressive and progressive disease. Genetic factors that define progression of neuroblastomas are still unknown. We performed comparative genomic hybridization (CGH) on 27 neuroblastomas and dual‐color fluorescence in situ hybridization (FISH) to identify genetic aberrations associated with progressive neuroblastoma showing resistance to aggressive treatment. 17q21–q25 gains and MYCN amplification were associated with stage 4 neuroblastomas; however, these genetic aberrations had no significant relation to the progression of stage 4 neuroblastomas. A novel chromosomal gain at 1q21–q25 was found in 8 of 16 cases (50%) of stage 4 neuroblastoma. Gain of 1q21–q25 was observed in all of the progressive cases (8/8), which showed resistance to chemotherapy, including 5 fatal neuroblastomas in stage 4, whereas 1q21–q25 gain was not found in any of the 8 remission cases in stage 4. Survival analysis also showed that 1q21–q25 gain was associated with a poor outcome. High xenotransplantability in nude mice was observed for the tumors with 1q21–q25 gain (4/5; 80%). These data show that 1q21–q25 gain is strongly associated with progression of stage 4 neuroblastoma. Furthermore, by dual‐color FISH analysis using cosmid clones, the 1q21–q25 gain was narrowed to increase in DNA copy number on 1q23 in the fatal type of stage 4 neuroblastoma showing this gain. These results suggest that DNA amplification at 1q23 may play a role in the development of progressive neuroblastoma in an advanced stage. Genes Chromosomes Cancer 25:261–269, 1999. © 1999 Wiley‐Liss, Inc.

Prognostic impact of chromosomal aberrations in Ewing tumours

“…Among the genetic parameters evaluated for prog- nostic clinical impact gain of 1q was a strong predictor for adverse OS and EFS both in patients with localised disease and in the entire study group. Gain of 1q has also been reported to be associated with advanced disease stage in two other childhood tumours, neuroblastoma (Hirai et al, 1999) and Wilms' tumour (Hing et al, 2001). 1q is known to contain several genes that might contribute to the development and/or progression of human sarcoma (Forus et al, 1998;Knuutila et al, 1998).…”

Pediatric Ependymoma: Biological Perspectives

“…1 and 3), justifying its further assessment as a prognostic marker in children. The gain of chromosome 1q is associated with an unfavorable outcome in Wilms' tumors, neuroblastomas, and Ewing's sarcomas, which suggests a generic role in pediatric tumor progression and recurrence (143)(144)(145). Conventional cytogenetics suggests that 1q gain results from a variety of unbalanced rearrangements with material from numerous partner chromosomes rather than a single, recurrent translocation (43,44).…”

WAVE3, an actin-polymerization gene, is truncated and inactivated as a result of a constitutional t(1;13)(q21;q12) chromosome translocation in a patient with ganglioneuroblastoma

“…The breakpoint on chromosome 1 was in a different position compared with the patients with stage 3, 4 and 4S. Recent reports suggest that amplification of this region is frequently seen in low-grade tumors and so may represent a subtype-specific gene locus for Nb (Hirai et al, 1999).…”