Examination of gene fusion status in archival samples of alveolar Rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study - III trial: A report from the children's oncology group

Frederic G. Barr, Lynette M Smith, James C. Lynch, Donna Strzelecki, David M. Parham, Stephen J. Qualman, Philip P. Breitfeld

Research output: Contribution to journalArticle

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Abstract

Alveolar rhabdomyosarcoma (ARMS) is a soft tissue cancer in which chromosomal translocations generate PAX3-FKHR and PAX7-FKHR gene fusions. To improve the approach for fusion detection in archival samples, we developed a real-time reverse transcriptase-polymerase chain reaction assay for these fusion transcripts. By incorporating consensus primers and gene-specific probes, both presence and subtype of the fusion were determined in one assay. We applied this approach to a convenience sample of 78 formalin-fixed, paraffin-embedded ARMS tumors from the intergroup Rhabdomyosarcoma Study (IRS)-III clinical trial and obtained satisfactory results in 59 (76%) cases. The distribution of fusion types was 35 (59%) PAX3-FKHR, 11 (19%) PAX7-FKHR, and 13 fusion-negative (22%). In a subsequent clinical analysis, we found that IRS-III ARMS cases analyzed for fusion status had a significantly improved outcome compared to IRS-III ARMS cases that were not available for fusion analysis. The basis of this outcome could not be explained by known prognostic clinical factors, and multivariate analysis confirmed that our convenience sample was not representative of the whole IRS-III cohort. In conclusion, although these robust assays provide new opportunities for correlative studies of archival material, our first application illustrates an important limitation of using a convenience sample for molecular-clinical correlative studies.

Original languageEnglish (US)
Pages (from-to)202-208
Number of pages7
JournalJournal of Molecular Diagnostics
Volume8
Issue number2
DOIs
StatePublished - May 2006

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Alveolar Rhabdomyosarcoma
Rhabdomyosarcoma
Gene Fusion
Genetic Translocation
Reverse Transcriptase Polymerase Chain Reaction
Paraffin
Formaldehyde
Statistical Factor Analysis
Real-Time Polymerase Chain Reaction
Neoplasms
Cohort Studies
Multivariate Analysis
Clinical Trials
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

Cite this

Examination of gene fusion status in archival samples of alveolar Rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study - III trial : A report from the children's oncology group. / Barr, Frederic G.; Smith, Lynette M; Lynch, James C.; Strzelecki, Donna; Parham, David M.; Qualman, Stephen J.; Breitfeld, Philip P.

In: Journal of Molecular Diagnostics, Vol. 8, No. 2, 05.2006, p. 202-208.

Research output: Contribution to journalArticle

Barr, Frederic G. ; Smith, Lynette M ; Lynch, James C. ; Strzelecki, Donna ; Parham, David M. ; Qualman, Stephen J. ; Breitfeld, Philip P. / Examination of gene fusion status in archival samples of alveolar Rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study - III trial : A report from the children's oncology group. In: Journal of Molecular Diagnostics. 2006 ; Vol. 8, No. 2. pp. 202-208.
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abstract = "Alveolar rhabdomyosarcoma (ARMS) is a soft tissue cancer in which chromosomal translocations generate PAX3-FKHR and PAX7-FKHR gene fusions. To improve the approach for fusion detection in archival samples, we developed a real-time reverse transcriptase-polymerase chain reaction assay for these fusion transcripts. By incorporating consensus primers and gene-specific probes, both presence and subtype of the fusion were determined in one assay. We applied this approach to a convenience sample of 78 formalin-fixed, paraffin-embedded ARMS tumors from the intergroup Rhabdomyosarcoma Study (IRS)-III clinical trial and obtained satisfactory results in 59 (76{\%}) cases. The distribution of fusion types was 35 (59{\%}) PAX3-FKHR, 11 (19{\%}) PAX7-FKHR, and 13 fusion-negative (22{\%}). In a subsequent clinical analysis, we found that IRS-III ARMS cases analyzed for fusion status had a significantly improved outcome compared to IRS-III ARMS cases that were not available for fusion analysis. The basis of this outcome could not be explained by known prognostic clinical factors, and multivariate analysis confirmed that our convenience sample was not representative of the whole IRS-III cohort. In conclusion, although these robust assays provide new opportunities for correlative studies of archival material, our first application illustrates an important limitation of using a convenience sample for molecular-clinical correlative studies.",
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