Detection of the ASPSCR1-TFE3 gene fusion in paraffin-embedded alveolar soft part sarcomas

Histopathology. 2007 Jun;50(7):881-6. doi: 10.1111/j.1365-2559.2007.02693.x.

Abstract

Aims: Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumour with unique morphology and a recurrent, non-reciprocal translocation der(17)t(X;17)(p11.2;q25) leading to the fusion of ASPSCR1 (also known as ASPL) to the transcription factor TFE3. Although diagnosis is straightforward in classical cases, tumours with atypical morphological features may be difficult to classify solely on the basis of conventional histopathology. The aim of this study was to analyse the chromosomal breakpoints in paraffin-embedded tissue.

Methods and results: Three male and two female ASPS patients including one case with uncommon histology were investigated by fluorescence in situ hybridization with split- and fusion-probes. The presence of the resulting ASPSCR1-TFE3 fusion transcripts was assessed by reverse transcriptase-polymerase chain reaction. Hybridization results showed a t(X;17)(p11.2;q25) in all tumours with a duplication of the telomeric part of chromosome Xp. In addition to wild-type TFE3, ASPSCR1-TFE3 fusion transcripts (three type 1 and two type 2 transcripts) were detected in all cases.

Conclusions: Molecular confirmation of ASPSCR1-TFE3 gene fusion is applicable to routinely processed archival and diagnostic tumour samples and aids in the differential diagnosis of ASPS.

MeSH terms

  • Adolescent
  • Adult
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Child, Preschool
  • Chromosomes, Human, Pair 17
  • Chromosomes, Human, X
  • DNA, Neoplasm / analysis
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Oncogene Fusion*
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Sarcoma, Alveolar Soft Part / genetics*
  • Sarcoma, Alveolar Soft Part / metabolism
  • Sarcoma, Alveolar Soft Part / secondary
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / metabolism
  • Soft Tissue Neoplasms / pathology

Substances

  • ASPSCR1 protein, human
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA, Neoplasm
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • TFE3 protein, human