Episomal Amplification of MYCN in a Case of Medulloblastoma

Overview

Journal Virchows Arch

Specialties Cell Biology
Molecular Biology
Pathology

Date 2008 Feb 21

PMID 18286303

Citations 2

Authors

Cecilia Surace

Florence Pedeutour

Domenico Trombetta

Fanny Burel-Vandenbos

Mariano Rocchi

Clelia Tiziana Storlazzi

Affiliations

Soon will be listed here.

Abstract

Gene amplification, in the form of double minutes (dmin) and/or homogeneously staining regions (hsr), is frequently associated with tumor development. A well-known example is neuroblastoma for which MYCN gene (v-myc myelocytomatosis viral-related oncogene) amplification has a relevant prognostic significance. A third cryptic form of amplification, cytogenetically invisible and composed of episomes, has been also described, but it is very rarely seen in primary tumors. In this paper, we report on MYCN amplification, in the form of episomes, in a case of medulloblastoma. Detailed fluorescence in situ hybridization and real-time quantitative polymerase chain reaction analyses revealed an amplified genomic segment of approximately 590 kb containing only the genes MYCN and N-cym (v-myc myelocytomatosis viral-related oncogene, neuroblastoma-derived opposite strand). To the best of our knowledge, this is the first report of a solid primary tumor showing MYCN amplification in the form of episomes.

Citing Articles

Advancements in Focal Amplification Detection in Tumor/Liquid Biopsies and Emerging Clinical Applications.

Arshadi A, Tolomeo D, Venuto S, Storlazzi C Genes (Basel). 2023; 14(6).

PMID: 37372484 PMC: 10298061. DOI: 10.3390/genes14061304.

Analysis of clock gene-miRNA correlation networks reveals candidate drivers in colorectal cancer.

Mazzoccoli G, Colangelo T, Panza A, Rubino R, Tiberio C, Palumbo O Oncotarget. 2016; 7(29):45444-45461.

PMID: 27323779 PMC: 5216733. DOI: 10.18632/oncotarget.9989.

References

Corvi R, Amler L, Savelyeva L, Gehring M, Schwab M . MYCN is retained in single copy at chromosome 2 band p23-24 during amplification in human neuroblastoma cells. Proc Natl Acad Sci U S A. 1994; 91(12):5523-7. PMC: 44028. DOI: 10.1073/pnas.91.12.5523. View

Chen Q, Bilke S, Wei J, Whiteford C, Cenacchi N, Krasnoselsky A . cDNA array-CGH profiling identifies genomic alterations specific to stage and MYCN-amplification in neuroblastoma. BMC Genomics. 2004; 5:70. PMC: 520814. DOI: 10.1186/1471-2164-5-70. View

Vogt N, Lefevre S, Apiou F, Dutrillaux A, Cor A, Leuraud P . Molecular structure of double-minute chromosomes bearing amplified copies of the epidermal growth factor receptor gene in gliomas. Proc Natl Acad Sci U S A. 2004; 101(31):11368-73. PMC: 509208. DOI: 10.1073/pnas.0402979101. View

Armstrong B, Krystal G . Isolation and characterization of complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc. Cell Growth Differ. 1992; 3(6):385-90. View

Lichter P, Tang C, Call K, Hermanson G, Evans G, Housman D . High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science. 1990; 247(4938):64-9. DOI: 10.1126/science.2294592. View

Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R . Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet. 2004; 36(10):1084-9. DOI: 10.1038/ng1425. View

Carroll S, DeRose M, Gaudray P, Moore C, Von Hoff D, Wahl G . Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. Mol Cell Biol. 1988; 8(4):1525-33. PMC: 363312. DOI: 10.1128/mcb.8.4.1525-1533.1988. View

Scott D, Elsden J, Pearson A, Lunec J . Genes co-amplified with MYCN in neuroblastoma: silent passengers or co-determinants of phenotype?. Cancer Lett. 2003; 197(1-2):81-6. DOI: 10.1016/s0304-3835(03)00086-7. View

Storlazzi C, Fioretos T, Paulsson K, Strombeck B, Lassen C, Ahlgren T . Identification of a commonly amplified 4.3 Mb region with overexpression of C8FW, but not MYC in MYC-containing double minutes in myeloid malignancies. Hum Mol Genet. 2004; 13(14):1479-85. DOI: 10.1093/hmg/ddh164. View

10.

Fruhwald M, ODorisio M, Rush L, Reiter J, Smiraglia D, WENGER G . Gene amplification in PNETs/medulloblastomas: mapping of a novel amplified gene within the MYCN amplicon. J Med Genet. 2000; 37(7):501-9. PMC: 1734623. DOI: 10.1136/jmg.37.7.501. View

11.

Schwab M, Amler L . Amplification of cellular oncogenes: a predictor of clinical outcome in human cancer. Genes Chromosomes Cancer. 1990; 1(3):181-93. DOI: 10.1002/gcc.2870010302. View

12.

Bayani J, Zielenska M, Marrano P, Kwan Ng Y, Taylor M, Jay V . Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping. J Neurosurg. 2000; 93(3):437-48. DOI: 10.3171/jns.2000.93.3.0437. View

13.

Savelyeva L, Schwab M . Amplification of oncogenes revisited: from expression profiling to clinical application. Cancer Lett. 2001; 167(2):115-23. DOI: 10.1016/s0304-3835(01)00472-4. View

14.

Eberhart C, Kratz J, Wang Y, Summers K, Stearns D, Cohen K . Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol. 2004; 63(5):441-9. DOI: 10.1093/jnen/63.5.441. View

15.

Storlazzi C, Fioretos T, Surace C, Lonoce A, Mastrorilli A, Strombeck B . MYC-containing double minutes in hematologic malignancies: evidence in favor of the episome model and exclusion of MYC as the target gene. Hum Mol Genet. 2006; 15(6):933-42. DOI: 10.1093/hmg/ddl010. View