Recurrent NCOA2 Gene Rearrangements in Congenital/Infantile Spindle Cell Rhabdomyosarcoma
Juan Miguel Mosquera, Andrea Sboner, Lei Zhang, Naoki Kitabayashi, Chung-Liang Chen, Yung Shao Sung, Morris Edelman, Mark A Rubin, Cristina R Antonescu. Weill Medical College of Cornell University, New York, NY; Memorial Sloan-Kettering Cancer Center, New York, NY; North Shore LIJ Health System, Flushing, NY
Background: Spindle cell rhabdomyosarcoma (RMS) is a rare form of RMS with different clinical characteristics and behavior between children and adult patients. Its genetic hallmark remains unknown and it is debatable if there is a pathogenetic relationship between the spindle cell and the so-called sclerosing RMS.
Design: We studied two pediatric and one adult spindle cell RMS by next generation RNA sequencing. Data was analyzed using FusionSeq, a modular computational tool for gene fusion discovery. Additional 14 spindle cell RMS (from 8 children and 6 adults) and 4 sclerosing RMS (from 2 children and 2 adults) were screened by FISH.
Results: SRF-NCOA2 gene fusion was detected in a spindle cell RMS from a posterior neck in a 7 month-old child. The fusion matched the tumor karyotype and was further confirmed by FISH and RT-PCR, which showed fusion of SRF exon 6 to NCOA2 exon 12. NCOA2 rearrangements were identified in 2 additional spindle cell RMS from a 3 month-old and a 4 week-old child, both arising in the chest wall. In the latter tumor, TEAD1 was identified by rapid amplification of cDNA ends (RACE) to be the NCOA2 gene fusion partner. All others were negative for NCOA2 rearrangement.
Conclusions: Despite similar histomorphology in adults and young children, these results suggest that spindle cell RMS is a heterogeneous disease genetically as well as clinically. Our findings also support a relationship between NCOA2-rearranged spindle cell RMS occurring in young childhood and the so-called congenital RMS, which often displays rearrangements at 8q13 locus (NCOA2).
Monday, March 4, 2013 9:00 AM
Proffered Papers: Section H1, Monday Morning