Prevalence of FOXO1 gene abnormalities in a group of round-cell rhabdomyosarcomas with alveolar morphology

Abstract

Rhabdomyosarcomas (RMS) are group of soft tissue malignant tumours predominantly childhood. Alveolar rhabdomyosarcoma (aRMS) is the second most common variant of RMS. The majority of aRMSs display a translocations of FOXO1 gene. Such tumours are aggressive, metastasize early and are associated with a worse prognosis for the patient. However, some aRMS cases are rhabdomyosarcomas without classic chromosomal rearrangements. These tumors also have alveolar morphology, but neoplastic cells lack the FOXO1 gene translocation. Such fusion-negative round-cell RMSs behave clinically differently and have a better prognosis. The aim of the present study was to assess the prevalence of FOXO1 gene rearrangements in the group of round cell rhabdomyosarcomas with alveolar morphology. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study group consisted of 250 formalin-fixed paraffin-embedded samples from patients with RMS. The cytogenetic study was performed by fluorescence in situ hybridization with a locus-specific identifier (LSI) for FOXO1 (13q14). The PAX3-FOXO1 (COSF247) and PAX7-FOXO1 (COSF287) fusion transcripts was detected by RT-PCR. In the study group 1 (аRMS), the rearrangement of PAX3/7-FOXO1 was detected in 44% of cases, in 32% of cases was detected a combined rearrangement with amplification of the 3' FOXO1. In one case, the amplification of the 3' end of the FOXO1 gene was detected without rearrangement; this sample was sent for additional PCR study, as a result of which the chimeric PAX3-FOXO1 transcript was detected. In 22% cases cytogenetic abnormalities were not found. has not been identified. In group 2 (embryonal RMS) we did not detect translocation. The group of round-cell PMCs is heterogeneous and is represented by three variants of genetic events that determine the disease prognosis. At the same time, FOXO1 gene abnormalities are not found in the RMS group with non-alveolar morphology.