Novel, Cloned Translocation Partner in Ewing Sarcoma Couples Its Function to Oncology
K Szuhai, M IJszenga, D de Jong, A Karseladze, HJ Tanke, PCW Hogendoorn. Leiden University Medical Center, Leiden, Netherlands; N. N. Blokhin Cancer Research Center3, Moscow, Russian Federation
Background: Ewing sarcoma (ES) is an aggressive -second most common- bone sarcoma in childhood. Characteristic t(11;22)(85-90%), or t(21;22)(5-10%), or rarer variant translocations with involvement of chromosome 22 (5%) are present. At the gene level the EWSR1 gene fuses with FLI1, ERG or other ETS transcription factor family members. So far no ES has been identified with fusion of the EWSR1 to transcription factors other than ETS.
Design: Using molecular tools such as multicolor FISH, and array-CGH a ring chromosome containing chromosome 20 and 22 was identified in 3 ES cases. The breakpoint was mapped with (fiber-)FISH, and reverse-transcriptase-PCR followed by sequencing of the fusion partners.
Results: Molecular karyotyping showed the translocation and amplification of chromosomes 20q13 and 22q12 regions. Cloning of the breakpoint showed an in frame fusion between EWSR1 and a novel, hitherto unidentified partner gene. The identified partner is a transcription factor that is not member of the ETS transcription factor family.
Conclusions: A new translocation involving EWS has been cloned. The identified transcription factor is not member of the ETS family nor directly observed thus far in oncogenesis. It has diagnostic implications for ES cases with rearrangements of the EWSR1 gene without known ETS partners especially in bone and soft tissue sarcomas diagnosed as Ewing-like sarcoma.
Category: Bone & Soft Tissue
Monday, March 9, 2009 1:00 PM
Poster Session II # 6, Monday Afternoon