Concomitant amplification and expression of PAX7-FKHR and MYCN in a human rhabdomyosarcoma cell line carrying a cryptic t(1;13)(p36;q14)

Cancer Genet Cytogenet. 2000 Sep;121(2):139-45. doi: 10.1016/s0165-4608(00)00258-2.

Abstract

Alveolar rhabdomyosarcoma (ARMS) is associated with the specific chromosomal translocation (2;13)(q35;q14) or its rarer variant t(1;13)(p36;q14), which produces the fusion gene PAX7-FKHR. Here we describe the human cell line RC2, derived from an ARMS, which harbors a cryptic t(1;13)(p36;q14) and concomitantly shows amplification of the PAX7-FKHR fusion gene and of the MYCN oncogene. The t(1;13) and MYCN oncogene were studied by standard cytogenetic analysis and molecular techniques. The reverse transcriptase polymerase chain reaction demonstrated the expression of PAX7-FKHR mRNA in RC2 cells, although karyotype analysis failed to demonstrate a t(1;13)(p36;q14) chromosomal translocation or a derivative 13 chromosome. Double minute chromosomes were detected in all the metaphases studied. Fluorescence in situ hybridization analysis revealed multiple copies of the PAX7-FKHR fusion gene localized exclusively on a subset of double minutes, whereas multiple copies of MYCN were identified on other double minute chromosomes. Southern-blot analysis demonstrated that RC2 cells contain approximately 20 copies of the MYCN oncogene. So far no continuous RMS cell line carrying the t(1;13)(p36;q14) has been described, and PAX7-FKHR and MYCN amplifications have always been reported to occur separately in rhabdomyosarcoma (RMS). The availability of an ARMS cell line that harbors the t(1;13)(p36;q14) constitutes a useful tool for further understanding the role of the PAX7-FKHR fusion gene in RMS oncogenesis and may improve knowledge of the possible relation between PAX7-FKHR and MYCN amplification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 1
  • Chromosomes, Human, Pair 13
  • DNA-Binding Proteins / genetics*
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Gene Amplification*
  • Gene Expression*
  • Genes, myc*
  • Homeodomain Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • PAX7 Transcription Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhabdomyosarcoma, Alveolar / genetics*
  • Transcription Factors / genetics*
  • Translocation, Genetic
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • PAX7 Transcription Factor
  • PAX7 protein, human
  • Transcription Factors