Gene amplification as doubleminutes or homogeneously staining regions in solid tumors: Origin and structure

Clelia Tiziana Storlazzi, Angelo Lonoce, Maria C. Guastadisegni, Domenico Trombetta, Pietro D'Addabbo, Giulia Daniele, Alberto L'Abbate, Gemma Macchia, Cecilia Surace, Klaas Kok, Reinhard Ullmann, Stefania Purgato, Orazio Palumbo, Massimo Carella, Peter F. Ambros, Mariano Rocchi

Research output: Contribution to journalArticle

Abstract

Double minutes (dmin) and homogeneously staining regions (hsr) are the cytogenetic hallmarks of genomic amplification in cancer. Different mechanisms have been proposed to explain their genesis. Recently, our group showed that the MYC-containing dmin in leukemia cases arise by excision and amplification (episome model). In the present paper we investigated 10 cell lines from solid tumors showing MYCN amplification as dmin or hsr. Particularly revealing results were provided by the two subclones of the neuroblastoma cell line STA-NB-10, one showing dmin-only and the second hsr-only amplification. Both subclones showed a deletion, at 2p24.3, whose extension matched the amplicon extension. Additionally, the amplicon structure of the dmin and hsr forms was identical. This strongly argues that the episome model, already demonstrated in leukemias, applies to solid tumors as well, and that dmin and hsr are two faces of the same coin. The organization of the duplicated segments varied from very simple (no apparent changes from the normal sequence) to very complex. MYCN was always overexpressed (significantly overexpressed in three cases). The fusion junctions, always mediated by nonhomologous end joining, occasionally juxtaposed truncated genes in the same transcriptional orientation. Fusion transcripts involving NBAS (also known as NAG), FAM49A, BC035112 (also known as NCRNA00276), and SMC6 genes were indeed detected, although their role in the context of the tumor is not clear.

Original languageEnglish
Pages (from-to)1198-1206
Number of pages9
JournalGenome Research
Volume20
Issue number9
DOIs
Publication statusPublished - Sep 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Gene amplification as doubleminutes or homogeneously staining regions in solid tumors: Origin and structure'. Together they form a unique fingerprint.

  • Cite this

    Storlazzi, C. T., Lonoce, A., Guastadisegni, M. C., Trombetta, D., D'Addabbo, P., Daniele, G., L'Abbate, A., Macchia, G., Surace, C., Kok, K., Ullmann, R., Purgato, S., Palumbo, O., Carella, M., Ambros, P. F., & Rocchi, M. (2010). Gene amplification as doubleminutes or homogeneously staining regions in solid tumors: Origin and structure. Genome Research, 20(9), 1198-1206. https://doi.org/10.1101/gr.106252.110