Research Article
MYCN Is the only highly expressed gene from the core amplified domain in human neuroblastomas
Jill L. Reiter,
Garrett M. Brodeur,
Jill L. Reiter
Division of Oncology, The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania
Search for more papers by this authorCorresponding Author
Garrett M. Brodeur
Division of Oncology, The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania
Division of Oncology, Suite 902-D, Children's Hospital of Philadelphia, Abramson Pediatric Research Center, 324 South 34th Street, Philadelphia, PA 19104–4318Search for more papers by this authorJill L. Reiter,
Garrett M. Brodeur,
Jill L. Reiter
Division of Oncology, The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania
Search for more papers by this authorCorresponding Author
Garrett M. Brodeur
Division of Oncology, The Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania
Division of Oncology, Suite 902-D, Children's Hospital of Philadelphia, Abramson Pediatric Research Center, 324 South 34th Street, Philadelphia, PA 19104–4318Search for more papers by this authorFirst published: 07 December 1998
Citations: 19
Abstract
MYCN amplification in neuroblastomas is strongly associated with advanced stages of disease and a poor prognosis. We have recently defined a 130 kb core region of the MYCN amplicon that is consistently amplified in neuroblastomas. However, it has been argued that other expressed sequences were coamplified with MYCN and, as a result, might contribute to the aggressive phenotype of MYCN-amplified neuroblastomas. Therefore, we have screened cosmids representing the core MYCN-amplified domain and surrounding DNA by using a differential hybridization approach to detect other amplified, highly expressed genes from this region. Our results suggest that MYCN is the only highly expressed gene consistently amplified in human neuroblastomas, and that the MYCN gene is likely to be the only selective marker for genomic amplification in these tumors. Genes Chromosomes Cancer 23:134–140, 1998. © 1998 Wiley-Liss, Inc.
References
-
Amler LC,
Schurmann J,
Schwab M
(1996)
The DDX1 gene maps within 400 kbp 5′ to MYCN and is frequently coamplified in human neuroblastoma.
Genes Chromosomes Cancer
15:
134–147.
10.1002/(SICI)1098-2264(199602)15:2<134::AID-GCC9>3.0.CO;2-4 CAS PubMed Web of Science® Google Scholar
- Biedler JL, Spengler BA (1976) A novel chromosome abnormality in human neuroblastoma and antifolate-resistant Chinese hamster cell lines in culture. J Natl Cancer Inst 57: 683–695.
- Blackwood EM, Eisenman RN (1991) Max: A helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science 251: 1211–1217.
-
Brannan CI,
Dees EC,
Ingram RS,
Tilghman SM
(1990)
The product of the H19 gene may function as an RNA.
Mol Cell Biol
10:
18–36.
10.1128/MCB.10.1.28 Google Scholar
- Brodeur GM (1995) Molecular basis for heterogeneity in human neuroblastomas. Eur J Cancer 31A: 505–510.
- Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224: 1121–1124.
- Brodeur GM, Maris JM, Yamashiro DJ, Hogarty MD, White PS (1997) Biology and genetics of human neuroblastomas. J Pediatr Hematol Oncol 19: 93–101.
- Brown CJ, Hendrich BD, Rupert JL, Lafreniere RG, Xing Y, Lawrence J, Willard HR (1992) The human XISTgene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell 71: 527–542.
- Chan HSL, Gallie BL, DeBoer G, Haddad G, Ikegaki N, Dimitroulakos J, Yeger H, Ling V (1997) MYCN protein expression as a predictor of neuroblastoma prognosis. Clin Cancer Res 3: 1699–1706.
- Cheng JM, Hiemstra JL, Schneider SS, Naumova A, Cheung N-KV, Cohn SL, Diller L, Sapienza C, Brodeur GM (1993) Preferential amplication of the paternal allele of the N-myc gene in human neuroblastomas. Nature Genet 4: 191–194.
- Corvi R, Savelyeva L, Amler L, Handgretinger R, Schwab M (1995a) Cytogenetic evolution of MYCN and MDM2 amplification in the neuroblastoma LS tumor and its cell line. Eur J Cancer 31A: 520–523.
- Corvi R, Savelyeva L, Breit S, Wenzel A, Handgretinger R, Barak J, Oren M, Amler L, Schwab M (1995b) Nonsyntenic amplification of MDM2 and MYCN in human neuroblastoma. Oncogene 10: 1081–1086.
- Devereux J, Haeberli P, Smithies O (1984) A comprehensive set of sequence analysis programs for the VAX. Nucl Acids Res 12: 387–395.
-
Feinberg AP,
Vogelstein B
(1983)
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
Anal Biochem
123:
6–13.
10.1016/0003-2697(83)90418-9 Google Scholar
- George RE, Kenyon RM, McGuckin AG, Malcolm AJ, Pearson ADJ, Lunec J (1996) Investigation of coamplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, synde-can-1, and a DEAD box gene, DDX1, with N-myc in neuroblastoma. Oncogene 12: 1583–1587.
- Goutbout R, Squire J (1993) Amplification of a DEAD box protein gene in retinoblastoma cell lines. Proc Natl Acad Sci USA 90: 7578–7582.
- Graham MY, Otani T, Boime I, Olson MV, Carle GF, Chaplin DD (1987) Cosmid mapping of the human chorionic gonadotropin (3) subunit genes by field-inversion gel electrophoresis. Nucl Acids Res 15: 4437–4448.
- Jinbo T, Iwamura Y, Kaneko M, Sawaguchi S (1989) Coamplification of the L-myc and N-myc oncogenes in a neuroblastoma cell line. Jpn J Cancer Res 80: 299–301.
- Kadomatsu K, Tomomura M, Muramatsu T (1988) cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid gestation period of mouse embryogenesis. Biochem Biophys Res Comm 151: 1312–1318.
- Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF (1991) The trk protoncogene product: A signal transducing receptor for nerve growth factor. Science 252: 554–558.
- Kohl NE, Kanda N, Schreck RR, Bruns G, Latt SA, Gilbert F, Alt FW (1983) Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 35: 359–367.
- Kuroda H, White PS, Sulman EP, Manohar CF, Reiter JL, Cohn SL, Brodeur GM (1996) Physical mapping of the DDX1 gene 340 kb 5′ of MYCN. Oncogene 13: 1561–1565, 1996.
- Mäkelä TP, Koskinen PJ, Vastrik I, Alitalo K (1992) Alternative forms of Max as enhancers or suppressors of myc-ras contransformations. Science 256: 373–377.
- Manohar CG, Salwen HR, Brodeur GM, Cohn SL (1995) Coamplifi-cation and concomitant high levels of expression of a DEAD box gene with MYCN in human neuroblastoma. Genes Chromosomes Cancer 14: 196–206.
- Montgomery KT, Melera PW (1988) Analysis of a novel locus frequently coamplified with N-myc in human neuroblastoma. Progr Clin Biol Res 271: 71–88.
- Nakagawara A, Arima M, Azar CG, Scavarda NJ, Brodeur GM (1992) Inverse relationship between TRK expression and N-myc amplification in human neuroblastomas. Cancer Res 52: 1364–1368.
- Nakagawara A, Milbrandt J, Muramatsu T, Deuel TF, Zhao H, Cnaan A, Brodeur GM (1995) Differential expression of pleiotrophin and midkine in advanced neuroblastomas. Cancer Res 55: 1792–1797.
- Nisen PD, Waber PG, Rich MA, Pierce S, Garvin JRJ, Gilbert F, Lanzkowsky P (1988) N-myc oncogene RNA expression in neuroblastoma. J Natl Cancer Inst 80: 1633–1637.
-
Noguchi T,
Akiyama K,
Yokoyama M,
Kanda N,
Matsunaga T,
Nishi Y
(1996)
Amplification of a DEAD box gene (DDX1) with the MYCN gene in neuroblastomas as a result of cosegregation of sequences flanking the MYCN locus.
Genes Chromosomes Cancer
15:
129–133.
10.1002/(SICI)1098-2264(199602)15:2<129::AID-GCC8>3.0.CO;2-5 CAS PubMed Web of Science® Google Scholar
- Oettinger HF, Streeter H, Lose E, Copeland NG, Gilbert DJ, Justice MJ, Jenkins NA, Mohandas T, Bernfield M (1991) Chromosome mapping of the murine syndecan gene. Genomics 11: 334–338.
- Owerbach D, Rutter WJ, Roberts JL, Whitfeld P, Shine J, Seeburg PH, Shows TB (1981) The proopiomelanocortin (adrenocorticotro-pin/β-lipotropin) gene is located on chromosome 2 in humans. Somat Cell Genet 7: 359–369.
-
Pandita A,
Godbout R,
Zielenska M,
Thorner P,
Bayani J,
Squire JA
(1997)
Relational mapping of MYCN andDDX1 in band 2p24 and analysis of amplicon arrays in double minute chromosomes and homogeneously staining regions by use of free chromatin FISH.
Genes Chromosomes Cancer
20:
243–252.
10.1002/(SICI)1098-2264(199711)20:3<243::AID-GCC4>3.0.CO;2-2 CAS PubMed Web of Science® Google Scholar
- Reiter JL, Brodeur GM (1996) High-resolution mapping of a 130–kb core region of the MYCN amplicon in neuroblastomas. Genomics 32: 97–103.
- Reynolds CP, Tomayko MM, Donner L, Helson L, Seeger RC, Triche TJ, Brodeur GM (1988) Biological classification of cell lines derived from human neuroblastoma extracranial neural tumors. Progr Clin Biol Res 271: 291–306.
- Schneider SS, Hiemstra JL, Zehnbauer BA, Taillon-Miller P, Le Paslier D, Vogelstein B, Brodeur GM (1992) Isolation and structural analysis of a 1.2–megabase N-myc amplicon from a human neuroblastoma. Mol Cell Biol 12: 5563–5570.
- Schwab M, Alitalo K, Klempnauer KH, Varmus HE, Bishop JM, Gilbert F, Brodeur G, Goldstein M, Trent JM (1983) Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature 305: 245–248.
- Schwab M, Varmus HE, Bishop JM (1985) Human N-myc gene contributes to neoplastic transformation of mammalian cells in culture. Nature 316: 160–162.
- Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, Hammond D (1985) Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. New Engl J Med 313: 1111–1116.
- Seeger RC, Wada R, Brodeur GM, Moss TJ, Bjork RL, Sousa L, Slamon DJ (1988) Expression of N-myc by neuroblastomas with one or multiple copies of the oncogene. Progr Clin Biol Res 271: 41–49.
- Shiloh Y, Shipley J, Brodeur GM, Bruns G, Korf B, Donlon T, Schreck RR, Seeger R, Sakai K, Latt SA (1985) Differential amplification, assembly and relocation of multiple DNA sequences in human neuroblastomas and neuroblastoma cell lines. Proc Natl Acad Sci USA 82: 3761–3765.
- Slavc I, Ellenbogen R, Jung W-H, Vawter GF, Kretschmar C, Grier H, Korf BR (1990) MYC gene amplification and expression in primary human neuroblastoma. Cancer Res 50: 1459–1463.
- Small MB, Hay N, Schwab M, Bishop JM (1987) Neoplastic transformation by the human gene N-myc. Mol Cell Biol 7: 1638–1645.
- Squire JA, Thorner PS, Weitzman S, Maggi JD, Dirks P, Doyle J, Hale M, Godbout R (1995) Coamplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma. Oncogene 10: 1417–1422.
- Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Buecker JL, Pittman DD, Kaufman RJ, Brown E, Shoemaker C, Orr EC, Amphlett GW, Foster WB, Coe ML, Knutson GJ, Fass DN, Hewick RM (1984) Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature 312: 342.
- Uberbacher EC, Mural RJ (1991) Locating protein-coding regions in human DNA sequences by a multiple sensor-neural network approach. Proc Natl Acad Sci USA 88: 11261–11265.
- Van Roy N, Forus A, Mykelbost O, Cheng NC, Versteeg R, Speleman F (1995) Identification of two distinct chromosome 12–derived amplification units in neuroblastoma cell line NGP. Cancer Genet Cytogenet 82: 151–154.
- Winqvist R, Mäkelä T, Seppanen P, Janne O, Alhonen-Hongisto L, Janne J, Grzeschik KH, Alitalo K (1986) Human ornithine decar-boxylase sequences map to chromosome regions 2pter→ p23 and 7cen→qter but are not coamplified with NMYC oncogene. Cytogenet Cell Genet 42: 133–140.
- Yancopoulos GD, Nisen PD, Tesfaye A, Kohl NE, Goldfarb MP, Alt FW (1985) N-myc can cooperate with ras to transform normal cells in culture. Proc Natl Acad Sci USA 82: 5455–5459.
