Comparative Genomic Hybridization: The Profile Of Chromosomal Imbalances In Rhabdomyosarcoma

Objective:To characterize the profiles of chromosome imbalance of rhabdomyosarcoma.To compare the different alterations between the subtypes according to their fusion gene situation,histological subgroups, histologia grading and clinical staging.Methods:Twenty-five primary rhabdomyosarcomas for which formalin-fixed,paraffin-embedded(FFPE) samples were available were collected from the archives of the Department of Pathology,Institute of Medical,Shihezi University and the People's Hospital of Xinjiang,China.Including 10 alveolar rhabdomyosarcoma cases,12 embryonal rhabdomyosarcoma cases,3 pleomorphic rhabdomyosarcoma cases,and two rhabdomyosarcoma cell lines(A204,alveolar type;RD,embryonal type)were collected for the study,either,a set of representative hematoxylin and eosin stained slides were marked with identifying numbers and reviewed individually by two pathologists blinded to all clinical information.Tumors were assessed in according with modern diagnostic criteria.To enrich the tumor cell population,sections with no more than 70%of tumor cell areas were subjected for microdissection mannully.We screened DNA copy number changes in whole genomes by CGH in 25 primary rhabdomyosarcomas and 2 rhabdomyosarcoma cell lines.Analyse according to histological type,pathologic grading,clinical staging,gender and age, respectively.All data were analyzed using the SPSS 13.0 software package(SPSS Inc.,Chicago,IL).Results:25 cases with rhabdomyosarcoma showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome.(1)The frequently gained chromosome arms of RMS were 2p,12q,6p,9q,10q,1p,2q,6q,8q,15q,18q,and the frequently lost chromosome arms of RMS were 3p,11p,6p.(2)The frequently gained chromosome arms of ARMS were 12q,2p,6,2q,4q,10q,15q;The frequently lost chromosome arms were 3p,6p,1q,5q.The frequently gained chromosome arms of ERMS were 7p,9q,2p,18q,1p,8q;The frequently lost chromosome arms were 11p.(3)The frequently gained chromosome arms of translocation associated RMS were 12q,2,6,10q,4q and 15q(＞30%),3p,6p,5q(＞30%)were the frequently loss chromosome arms;The frequently gained chromosome arms of non-translocation associated RMS were 2p,9q,18q(＞30%),and 11p,14q(＞30%)were the frequently loss chromosome arms of this kind of RMS.Gains of 12q significantly correlated with translocation type(P＜0.05).(4)Gains of 9q was significantly correlated with clinical staging(P＜0.05).Conclusions These observations suggest that:(1)2p,12q,6p,9q,10q,1p,2q,6q,8q,15q,18q gained and 3p,11p,6p loss may correlated with RMS-related carcinogenesis;(2)gains of 12q may correlated with translocation;(3)gains of 9q may correlated with early stage of RMS,and gains of 6p may correlated with later satge of RMS.