This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fong, C.-t. Articles by Brodeur, G. M. Search for Related Content PubMed PubMed Citation Articles by Fong, C.-t. Articles by Brodeur, G. M.

Loss of Heterozygosity for Chromosomes 1 or 14 Defines Subsets of Advanced Neuroblastomas¹

Department of Pediatrics, Washington University School of Medicine, and the Pediatric Oncology Group (POG), St. Louis, Missouri 63110 [C-t. F., P. S. W., G. M. B.]; Ludwig Institute for Cancer Research, Montreal, Quebec, H3A-1A1, Canada [K. P., C. S., W. K. C.]; Departments of Oncology [S. E. K., B. V.] and Pathology [S. E. K.], Johns Hopkins University, Baltimore, Maryland 21205; POG Statistics Office, Gainesville, Florida 32608 [A. B. C.]; and Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105 [A. T. L.]

Neuroblastomas have been characterized genetically by N-myc amplification and by deletions or loss of heterozygosity (LOH) for the short arm of chromosome 1. However, recent studies have suggested deletion or allelic loss involving at least three other chromosome arms, 11q, 14q, and 17p. Therefore, we undertook an analysis of allelic loss for these respective chromosomal arms to determine the frequency and pattern of LOH as well as the correlation of these findings with other biological and clinical variables. A group of 24 pairs of normal and tumor DNAs was chosen that were representative of patients of different ages and stages. A substantial frequency of LOH (20%) was found only for 1p and 14q, whereas LOH for the other chromosome arms occurred in 5% of cases. On the basis of these results, we extended the analysis to a total of 59 neuroblastomas, and we found 1p LOH in 15 of the 59 cases (25%) and 14q LOH in 10 of 43 informative cases (23%). N-myc amplification was found in 15 of the 59 cases (25%). This analysis confirmed that 1p LOH and 14q LOH occurred almost exclusively in patients with advanced stages of disease. Furthermore, LOH for 1p and 14q usually occurred independent of each other, and 1p LOH frequently was associated with N-myc amplification, whereas 14q LOH was not. Thus, our results demonstrate that neuroblastomas are complex genetically and that there are at least two distinct loci for putative suppressor genes that are deleted independently in this tumor, both of which are associated with advanced stages of disease.

¹ This work was supported in part by NIH Grants CA-39771 and CA-05587 (G. M. B.), NCI-Canada (C. S.), and CA-43460 and CA-35494 (B. V.).

² Present address: Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642.

³ Present address: Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92003.

⁴ To whom requests for reprints should be addressed, at Department of Pediatrics, Washington University School of Medicine, 400 South Kingshighway Boulevard, St. Louis, MO 63110.

Received 10/ 9/91. Accepted 1/27/92.

This article has been cited by other articles:

				T Hienonen, H Sammalkorpi, P Isohanni, R Versteeg, R Karikoski, and L A Aaltonen A 17p11.2 germline deletion in a patient with Smith-Magenis syndrome and neuroblastoma J. Med. Genet., January 1, 2005; 42(1): e3 - e3. [Full Text] [PDF]

				I.M. Ambros, J. Benard, M. Boavida, N. Bown, H. Caron, V. Combaret, J. Couturier, C. Darnfors, O. Delattre, J. Freeman-Edward, et al. Quality Assessment of Genetic Markers Used for Therapy Stratification J. Clin. Oncol., June 1, 2003; 21(11): 2077 - 2084. [Abstract] [Full Text] [PDF]

				J. Mora, N.-K. V. Cheung, S. Oplanich, L. Chen, and W. L. Gerald Novel Regions of Allelic Imbalance Identified by Genome-wide Analysis of Neuroblastoma Cancer Res., March 1, 2002; 62(6): 1761 - 1767. [Abstract] [Full Text] [PDF]

				N Bown Neuroblastoma tumour genetics: clinical and biological aspects J. Clin. Pathol., December 1, 2001; 54(12): 897 - 910. [Abstract] [Full Text] [PDF]

				M. Lastowska, C. Cullinane, S. Variend, S. Cotterill, N. Bown, S. O'Neill, K. Mazzocco, P. Roberts, J. Nicholson, C. Ellershaw, et al. Comprehensive Genetic and Histopathologic Study Reveals Three Types of Neuroblastoma Tumors J. Clin. Oncol., June 15, 2001; 19(12): 3080 - 3090. [Abstract] [Full Text] [PDF]

				J. Mora, W. L. Gerald, J. Qin, and N.-K. V. Cheung Molecular Genetics of Neuroblastoma and the Implications for Clinical Management: A Review of the MSKCC Experience Oncologist, June 1, 2001; 6(3): 263 - 268. [Abstract] [Full Text] [PDF]

				J. M. Maris, M. J. Weiss, C. Guo, R. B. Gerbing, D. O. Stram, P. S. White, M. D. Hogarty, E. P. Sulman, P. M. Thompson, J. N. Lukens, 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 J. Clin. Oncol., May 9, 2000; 18(9): 1888 - 1899. [Abstract] [Full Text] [PDF]

				W. A. Weiss, T. Godfrey, C. Francisco, and J. M. Bishop Genome-wide Screen for Allelic Imbalance in a Mouse Model for Neuroblastoma Cancer Res., May 1, 2000; 60(9): 2483 - 2487. [Abstract] [Full Text]

				J. Mora, N.-K. V. Cheung, B. H. Kushner, M. P. LaQuaglia, K. Kramer, M. Fazzari, G. Heller, L. Chen, and W. L. Gerald Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p J. Mol. Diagn., February 1, 2000; 2(1): 37 - 46. [Abstract] [Full Text]

				J. M. Maris and K. K. Matthay Molecular Biology of Neuroblastoma J. Clin. Oncol., July 1, 1999; 17(7): 2264 - 2264. [Abstract] [Full Text] [PDF]

				E. Hiyama, K. Hiyama, T. Yokoyama, I. Fukuba, H. Yamaoka, J. W. Shay, and Y. Matsuura Rapid Detection of MYCN Gene Amplification and Telomerase Expression in Neuroblastoma Clin. Cancer Res., March 1, 1999; 5(3): 601 - 609. [Abstract] [Full Text] [PDF]

				J. K. Simpson and M. N. Gaze Current Management of Neuroblastoma Oncologist, August 1, 1998; 3(4): 253 - 262. [Abstract] [Full Text]

				S. Huang, G. Shao, and L. Liu The PR Domain of the Rb-binding Zinc Finger Protein RIZ1 Is a Protein Binding Interface and Is Related to the SET Domain Functioning in Chromatin-mediated Gene Expression J. Biol. Chem., June 26, 1998; 273(26): 15933 - 15939. [Abstract] [Full Text] [PDF]

				E. H. Radany, K. Hong, S. Kesharvarzi, E. S. Lander, and J. M. Bishop Mouse mammary tumor virus/v-Ha-ras transgene-induced mammary tumors exhibit strain-specific allelic loss on mouse chromosome 4 PNAS, August 5, 1997; 94(16): 8664 - 8669. [Abstract] [Full Text] [PDF]

				H. Caron, P. van Sluis, J. de Kraker, J. Bokkerink, M. Egeler, G. Laureys, R. Slater, A. Westerveld, P.A. VoUte, and R. Versteeg Allelic Loss of Chromosome 1p as a Predictor of Unfavorable Outcome in Patients with Neuroblastoma N. Engl. J. Med., January 25, 1996; 334(4): 225 - 230. [Abstract] [Full Text] [PDF]