Gene Copy Number Abnormalities Detected by FISH in Soft Tissue Tumors Typically Associated with Recurrent Fusion Proteins
LM Sholl, P Dal Cin, CR Antonescu, CD Fletcher. Brigham and Women's Hospital, Boston, MA; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Recurrent chromosomal translocations are common cytogenetic aberrations in soft tissue tumors, and as such have become reliable diagnostic tools. In practice, tumor karyotype is often not routinely performed and we may rely on FISH for detecting specific gene rearrangements. Occasionally, tumors with classic morphology lack the expected rearrangement by FISH but instead show copy number changes of the probed locus. Aside from a few well-described examples, including amplified tumor genes forming rings in dedifferentiated liposarcoma and DFSP, copy number abnormality is not a well-recognized mechanism of tumorigenesis in sarcomas.
Design: We retrieved ten cases that were found to have copy number changes by FISH, including four cases of low grade fibromyxoid sarcoma (LGFMS), one case of extraskeletal myxoid chondrosarcoma (EMCS), three cases of myxoid liposarcoma (MLS), one case of infantile fibrosarcoma, and one case of angiomatoid MFH (AMFH). All cases were reviewed by two soft tissue experts. FISH for FUS, EWS, ETV6, and CHOP was performed on 50 micron paraffin-embedded tissue sections using commercially available break-apart probes.
Results: Four cases of LGFMS contained 3-4 copies of the FUS gene without evidence of rearrangement. One case of AMFH contained 3-4 copies of FUS and centromeric 16 without evidence of rearrangement. One case of infantile fibrosarcoma contained 3 copies of ETV6 and centromeric 12 without evidence of rearrangement. One case of MLS contained 3 to 8 copies of CHOP without evidence of rearrangement. One case of EMCS contained 3-5 copies of the rearranged EWS gene by FISH. Two cases (both high grade myxoid liposarcoma) demonstrated high level amplification: one case contained an amplified CHOP-EWSR1 fusion gene and the other showed amplification of the region of 12q containing CHOP.
Conclusions: A subset of sarcomas with classic morphology lacks the expected underlying translocation but instead harbors copy number alterations of one of the predicted fusion gene partners. Polysomy or amplification involving the fusion gene can also occur and may be dependent on tumor grade. The significance of this observation is unclear but it may potentially cause diagnostic confusion.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 14, Monday Afternoon