No evidence for the presence of an imprinted neuroblastoma suppressor gene within chromosome sub-band 1p36.3.

Deletion of the distal short arm of chromosome 1 occurs in 35% of primary neuroblastomas (NBs). These deletions tend to be large and extend to the telomere, but a common region within sub-band 1p36.3 is consistently lost. Despite intensive investigation, no candidate tumor suppressor gene within this region has been shown to undergo tumor-specific mutation consistent with biallelic inactivation. In addition, initial studies demonstrated preferential loss of the maternally inherited 1p homologue in NBs with 1p loss of heterozygosity (LOH) without MYCN amplification. This has led to the widely accepted hypothesis that a genomically imprinted NB suppressor gene is the target of 1p deletion in this subset. To test this hypothesis we have studied 293 primary NBs for LOH within 1p36.3 and determined the parental origin of the deleted 1p homologue. LOH within 1p36.3 was demonstrated in 55 NBs (19%). Of these, 29 occurred in tumors without MYCN amplification: 13 had deletion of the maternally inherited 1p, whereas 16 had deletion of the paternally inherited 1p (P = 0.58). These data strongly refute a parent-of-origin effect for 1p deletions in NB and exclude the existence of an imprinted NB suppressor locus in this region.

[1]  M. Schwab,et al.  Smallest region of overlapping deletion in 1p36 in human neuroblastoma: A 1 Mbp cosmid and PAC contig , 2001, Genes, chromosomes & cancer.

[2]  R. Versteeg,et al.  Chromosome bands 1p35–36 contain two distinct neuroblastoma tumor suppressor loci, one of which is imprinted , 2001, Genes, chromosomes & cancer.

[3]  J. Maris,et al.  Identification of a 1-megabase consensus region of deletion at 1p36.3 in primary neuroblastomas. , 2000, Medical and pediatric oncology.

[4]  M. Hattori,et al.  Identification of the homozygously deleted region at chromosome 1p36.2 in human neuroblastoma. , 2000, Medical and pediatric oncology.

[5]  D. Stram,et al.  Loss of heterozygosity at 1p36 independently predicts for disease progression but not decreased overall survival probability in neuroblastoma patients: a Children's Cancer Group study. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  A. Hoffman,et al.  Allelic expression of the putative tumor suppressor gene p73 in human fetal tissues and tumor specimens. , 2000, Biochimica et biophysica acta.

[7]  K K Matthay,et al.  The International Neuroblastoma Pathology Classification (the Shimada system) , 1999, Cancer.

[8]  P. Kogner,et al.  Variable expression and absence of mutations in p73 in primary neuroblastoma tumors argues against a role in neuroblastoma development. , 1999, International journal of molecular medicine.

[9]  J W Gray,et al.  NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Swendeman,et al.  Expression level, allelic origin, and mutation analysis of the p73 gene in neuroblastoma tumors and cell lines. , 1998, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[11]  A. Yang,et al.  Monoallelically Expressed Gene Related to p53 at 1p36, a Region Frequently Deleted in Neuroblastoma and Other Human Cancers , 1997, Cell.

[12]  D. Barlow,et al.  Gametic Imprinting in Mammals , 1995, Science.

[13]  F. Hedborg,et al.  Deletion of chromosome 1p loci and microsatellite instability in neuroblastomas analyzed with short-tandem repeat polymorphisms. , 1995, Cancer research.

[14]  A T Look,et al.  A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2-36.3. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  F. Berthold,et al.  Revisions of the international criteria for neuroblastoma diagnosis, staging and response to treatment. , 1993, Progress in clinical and biological research.

[16]  Rogier Versteeg,et al.  Allelic loss of chromosome 1p36 in neuroblastoma is of preferential maternal origin and correlates with N–myc amplification , 1993, Nature Genetics.

[17]  E. Stanbridge,et al.  Dissociation of suppression of tumorigenicity and differentiation in vitro effected by transfer of single human chromosomes into human neuroblastoma cells. , 1991, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[18]  F. Speleman,et al.  Constitutional translocation t(1;17)(p36;q12–21) in a patient with neuroblastoma , 1990, Genes, chromosomes & cancer.

[19]  F. Berthold,et al.  Neuroblastoma consensus deletion maps to 1p36.1–2 , 1989, Genes, chromosomes & cancer.

[20]  N C Dracopoli,et al.  Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastomas: correlation with N-myc amplification. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[21]  G. S. Sekhon,et al.  Chromosomal aberrations in human neuroblastomas , 1977, Cancer.

[22]  A. Look,et al.  Detection of MYCN gene amplification in neuroblastoma by fluorescence in situ hybridization: a pediatric oncology group study. , 2001, Neoplasia.

[23]  J. Maris,et al.  Analysis of genomic imprinting at 1p35-36 in neuroblastoma. , 2001, Medical and pediatric oncology.

[24]  I M Morison,et al.  The imprinted gene and parent-of-origin effect database , 2001, Nucleic Acids Res..

[25]  P. Ambros,et al.  Fine mapping of a tumour suppressor candidate gene region in 1p36.2-3, commonly deleted in neuroblastomas and germ cell tumours. , 2001, Medical and pediatric oncology.

[26]  T. Matise,et al.  Detailed molecular analysis of 1p36 in neuroblastoma. , 2001, Medical and pediatric oncology.

[27]  E. Zackai,et al.  Constitutional 1p36 deletion in a child with neuroblastoma. , 1993, American journal of human genetics.