title: Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma.
abstract: Spindle cell rhabdomyosarcoma (RMS) is a rare form of RMS with different clinical characteristics between children and adult patients. Its genetic hallmark remains unknown and it remains debatable if there is pathogenetic relationship between the spindle cell and the so-called sclerosing RMS. We studied two pediatric and one adult spindle cell RMS by next generation RNA sequencing and FusionSeq data analysis to detect novel fusions. An SRF-NCOA2 fusion was detected in a spindle cell RMS from the posterior neck in a 7-month-old child. The fusion matched the tumor karyotype and was confirmed by FISH and RT-PCR, which showed fusion of SRF exon 6 to NCOA2 exon 12. Additional 14 spindle cell (from 8 children and 6 adults) and 4 sclerosing (from 2 children and 2 adults) RMS were tested by FISH for the presence of abnormalities in NCOA2, SRF, as well as for PAX3 and NCOA1. NCOA2 rearrangements were found in two additional spindle cell RMS from a 3-month-old and a 4-week-old child. In the latter tumor, TEAD1 was identified by rapid amplification of cDNA ends (RACE) to be the NCOA2 gene fusion partner. None of the adult tumors were positive for NCOA2 rearrangement. 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).
authors: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10065, USA. jmm9018@med.cornell.edu
authors: Juan Miguel
authors: JM
authors: Mosquera
authors: Andrea
authors: A
authors: Sboner
authors: Lei
authors: L
authors: Zhang
authors: Naoki
authors: N
authors: Kitabayashi
authors: Chun-Liang
authors: CL
authors: Chen
authors: Yun Shao
authors: YS
authors: Sung
authors: Leonard H
authors: LH
authors: Wexler
authors: Michael P
authors: MP
authors: LaQuaglia
authors: Morris
authors: M
authors: Edelman
authors: Chandrika
authors: C
authors: Sreekantaiah
authors: Mark A
authors: MA
authors: Rubin
authors: Cristina R
authors: CR
authors: Antonescu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018331:Nevus, Spindle Cell / Q000473:pathology*; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics*; D011379:Prognosis; D012208:Rhabdomyosarcoma / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2