Enhanced Expression of the Human Gene N-myc Consequent to Amplification of DNA May Contribute to Malignant Progression of Neuroblastoma

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1984 Aug 1

PMID 6589638

Citations 94

Authors

M Schwab

J Ellison

M Busch

W Rosenau

H E Varmus

J M Bishop

Affiliations

Soon will be listed here.

Abstract

Previous studies had revealed that DNA with partial similarity to the myc oncogene (N-myc) is frequently amplified in human neuroblastoma cell lines and neuroblastoma tumors. We show here for one patient that N-myc amplification is confined to the neuroblastoma tumor and is not present in normal tissue. N-myc mRNA approximately equal to 4.0 kilobases in size is detectable in neuroblastoma cell lines and tumors and in a retinoblastoma cell line. By contrast, appreciable amounts of this RNA were not present in a number of cell lines derived from other human tumors and in fibroblasts from a normal individual and from a neuroblastoma patient. Low levels of N-myc RNA were found in human and murine neuroblastoma cell lines lacking amplification of this gene, up to 80-fold greater levels in all cell lines carrying amplified N-myc. In situ hybridization to sections of neuroblastoma tumors revealed high expression of N-myc predominantly in undifferentiated neuroblasts. We hypothesize that amplification and consequent elevated expression of N-myc may be related to malignant progression.

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References

Levan A, MANOLOV G, Clifford P . Chromosomes of a human neuroblastoma: a new case with accessory minute chromosomes. J Natl Cancer Inst. 1968; 41(6):1377-87. View

Cox D, YUNCKEN C, Spriggs A . MINUTE CHROMATIN BODIES IN MALIGNANT TUMOURS OF CHILDHOOD. Lancet. 1965; 1(7402):55-8. DOI: 10.1016/s0140-6736(65)90131-5. View

Biedler J, Spengler B . Metaphase chromosome anomaly: association with drug resistance and cell-specific products. Science. 1976; 191(4223):185-7. DOI: 10.1126/science.942798. View

Balaban-Malenbaum G, Gilbert F . Double minute chromosomes and the homogeneously staining regions in chromosomes of a human neuroblastoma cell line. Science. 1977; 198(4318):739-41. DOI: 10.1126/science.71759. View

Schimke R, Kaufman R, Alt F, Kellems R . Gene amplification and drug resistance in cultured murine cells. Science. 1978; 202(4372):1051-5. DOI: 10.1126/science.715457. View

Brahic M, Haase A . Detection of viral sequences of low reiteration frequency by in situ hybridization. Proc Natl Acad Sci U S A. 1978; 75(12):6125-9. PMC: 393131. DOI: 10.1073/pnas.75.12.6125. View

Collins S, Groudine M . Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line. Nature. 1982; 298(5875):679-81. DOI: 10.1038/298679a0. View

Dalla-Favera R, Wong-Staal F, Gallo R . Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient. Nature. 1982; 299(5878):61-3. DOI: 10.1038/299061a0. View

Klein G . Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell. 1983; 32(2):311-5. DOI: 10.1016/0092-8674(83)90449-x. View

10.

Franke F, Lampert F . [Chromosomal studies in metastatic neuroblastoma]. Onkologie. 1982; 5(6):268-72. DOI: 10.1159/000215020. View

11.

Alitalo K, Schwab M, Lin C, Varmus H, Bishop J . Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci U S A. 1983; 80(6):1707-11. PMC: 393672. DOI: 10.1073/pnas.80.6.1707. View

12.

Becker L, Hinton D . Primitive neuroectodermal tumors of the central nervous system. Hum Pathol. 1983; 14(6):538-50. DOI: 10.1016/s0046-8177(83)80006-9. View

13.

Schwab M, Alitalo K, Varmus H, Bishop J, George D . A cellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumour cells. Nature. 1983; 303(5917):497-501. DOI: 10.1038/303497a0. View

14.

Collins S, Groudine M . Rearrangement and amplification of c-abl sequences in the human chronic myelogenous leukemia cell line K-562. Proc Natl Acad Sci U S A. 1983; 80(15):4813-7. PMC: 384135. DOI: 10.1073/pnas.80.15.4813. View

15.

Schwab M, Alitalo K, Klempnauer K, Varmus H, Bishop J, Gilbert F . Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983; 305(5931):245-8. DOI: 10.1038/305245a0. View

16.

Bishop J . Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983; 52:301-54. DOI: 10.1146/annurev.bi.52.070183.001505. View

17.

Casper J, Trent J, Harb J, Piaskowski V, Helmsworth M, Finlan J . Distinguishing characteristics of a new neuroblastoma cell line. Cancer Genet Cytogenet. 1983; 10(2):177-86. DOI: 10.1016/0165-4608(83)90122-x. View

18.

Leder P, Battey J, Lenoir G, Moulding C, Murphy W, Potter H . Translocations among antibody genes in human cancer. Science. 1983; 222(4625):765-71. DOI: 10.1126/science.6356357. View

19.

Little C, Nau M, Carney D, Gazdar A, Minna J . Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983; 306(5939):194-6. DOI: 10.1038/306194a0. View

20.

Kohl N, Kanda N, Schreck R, Bruns G, LATT S, Gilbert F . Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 1983; 35(2 Pt 1):359-67. DOI: 10.1016/0092-8674(83)90169-1. View