Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions

Frederic G. Barr, Stephen J. Qualman, Michele H. Macris, Natalya Melnyk, Elizabeth R. Lawlor, Donna M. Strzelecki, Timothy J. Triche, Julia A. Bridge, Poul H B Sorensen

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Abstract

Previous studies of the PAX3-FKHR and PAX7-FKHR gene fusions in alveolar rhabdomyosarcoma (ARMS) indicated that the corresponding fusion transcripts are not detectable in 20% of ARMS cases. To investigate the genetic features of this ARMS subset, we identified 23 ARMS cases in which PAX3-FKHR and PAX7-FKHR transcripts were not detected by a standard sensitivity reverse transcription-PCR (RT-PCR) assay. Subsequent analysis with a high sensitivity RT-PCR assay identified low-level expression of PAX3-FKHR or PAX7-FKHR in three cases. Analysis with a Southern blot assay for PAX3 and PAX7 rearrangements and a fluorescence in situ hybridization assay for FKHR rearrangements identified three cases with variant fusions in which PAX3 or PAX7 is postulated to be joined to novel genomic loci. In one such case, RT-PCR analysis of candidate partners identified a fusion of PAX3 to AFX, which is highly similar in structure and function to FKHR. Additional fluorescence in situ hybridization analysis identified two cases in which a PAX3-FKHR or PAX7-FKHR genomic fusion is present but is not associated with a fusion transcript detectable by RT-PCR. Finally, our analyses of the PAX3, PAX7, and FKHR loci did not identify rearrangements in >50% of cases, consistent with the possibility that there is a true fusion-negative subset. In summary, our analysis of ARMS cases without characteristic PAX3-FKHR or PAX7-FKHR transcripts identified several genetically distinct subsets including low expression or atypical presentation of standard fusions, variant fusions with other genes, and possibly true fusionnegative cases.

Original languageEnglish (US)
Pages (from-to)4704-4710
Number of pages7
JournalCancer Research
Volume62
Issue number16
StatePublished - Aug 15 2002

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Alveolar Rhabdomyosarcoma
Genetic Heterogeneity
Gene Fusion
Reverse Transcription
Polymerase Chain Reaction
Fluorescence In Situ Hybridization
Southern Blotting
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Barr, F. G., Qualman, S. J., Macris, M. H., Melnyk, N., Lawlor, E. R., Strzelecki, D. M., ... Sorensen, P. H. B. (2002). Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. Cancer Research, 62(16), 4704-4710.

Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. / Barr, Frederic G.; Qualman, Stephen J.; Macris, Michele H.; Melnyk, Natalya; Lawlor, Elizabeth R.; Strzelecki, Donna M.; Triche, Timothy J.; Bridge, Julia A.; Sorensen, Poul H B.

In: Cancer Research, Vol. 62, No. 16, 15.08.2002, p. 4704-4710.

Research output: Contribution to journalArticle

Barr, FG, Qualman, SJ, Macris, MH, Melnyk, N, Lawlor, ER, Strzelecki, DM, Triche, TJ, Bridge, JA & Sorensen, PHB 2002, 'Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions', Cancer Research, vol. 62, no. 16, pp. 4704-4710.
Barr FG, Qualman SJ, Macris MH, Melnyk N, Lawlor ER, Strzelecki DM et al. Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. Cancer Research. 2002 Aug 15;62(16):4704-4710.
Barr, Frederic G. ; Qualman, Stephen J. ; Macris, Michele H. ; Melnyk, Natalya ; Lawlor, Elizabeth R. ; Strzelecki, Donna M. ; Triche, Timothy J. ; Bridge, Julia A. ; Sorensen, Poul H B. / Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusions. In: Cancer Research. 2002 ; Vol. 62, No. 16. pp. 4704-4710.
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abstract = "Previous studies of the PAX3-FKHR and PAX7-FKHR gene fusions in alveolar rhabdomyosarcoma (ARMS) indicated that the corresponding fusion transcripts are not detectable in 20{\%} of ARMS cases. To investigate the genetic features of this ARMS subset, we identified 23 ARMS cases in which PAX3-FKHR and PAX7-FKHR transcripts were not detected by a standard sensitivity reverse transcription-PCR (RT-PCR) assay. Subsequent analysis with a high sensitivity RT-PCR assay identified low-level expression of PAX3-FKHR or PAX7-FKHR in three cases. Analysis with a Southern blot assay for PAX3 and PAX7 rearrangements and a fluorescence in situ hybridization assay for FKHR rearrangements identified three cases with variant fusions in which PAX3 or PAX7 is postulated to be joined to novel genomic loci. In one such case, RT-PCR analysis of candidate partners identified a fusion of PAX3 to AFX, which is highly similar in structure and function to FKHR. Additional fluorescence in situ hybridization analysis identified two cases in which a PAX3-FKHR or PAX7-FKHR genomic fusion is present but is not associated with a fusion transcript detectable by RT-PCR. Finally, our analyses of the PAX3, PAX7, and FKHR loci did not identify rearrangements in >50{\%} of cases, consistent with the possibility that there is a true fusion-negative subset. In summary, our analysis of ARMS cases without characteristic PAX3-FKHR or PAX7-FKHR transcripts identified several genetically distinct subsets including low expression or atypical presentation of standard fusions, variant fusions with other genes, and possibly true fusionnegative cases.",
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AU - Macris, Michele H.

AU - Melnyk, Natalya

AU - Lawlor, Elizabeth R.

AU - Strzelecki, Donna M.

AU - Triche, Timothy J.

AU - Bridge, Julia A.

AU - Sorensen, Poul H B

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