title: Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma.
abstract: Somatic mutations in the ARID1A tumor-suppressor gene have been frequently identified in ovarian clear cell carcinoma (CCC) cases. BAF250a encoded by ARID1A is a member of the SWI/SNF complex, but the expression and mutation status of other SWI/SNF subunits have not been explored. The current study aimed to elucidate the biological and clinical significance of the SWI/SNF complex subunits, by assessing the expression and mutation status of SWI/SNF subunits, and distinct genomic aberrations associated with their expression. Of 82 CCC specimens, 38 samples presented no BAF250a expression, and 50 samples exhibited the loss of at least one subunit of the SWI/SNF complex. Cases which lack at least one SWI/SNF complex component exhibited significantly more advanced stages, faster growth and stronger nuclear atypia compared with SWI/SNF-positive samples (p<0.05). Although BAF250a expression is not related to poor prognosis, the group presenting the loss of at least one SWI/SNF complex subunit exhibited significantly shorter overall and progression-free survivals (p<0.05). A multivariate analysis suggested that the expression status of the SWI/SNF complex serves as an independent prognostic factor (p<0.005). The cases positive for all SWI/SNF subunits demonstrated significantly greater DNA copy number alterations, such as amplification at chromosomes 8q.24.3 and 20q.13.2-20q.13.33 (including ZNF217) and deletion at chromosomes 13q12.11-13q14.3 (including RB1), 17p13.2-17p13.1 (including TP53) and 19p13.2-19p13.12. In conclusion, the CCCs exhibiting the loss of one or multiple SWI/SNF complex subunits demonstrated aggressive behaviors and poor prognosis, whereas the CCCs with positive expression for all SWI/SNF components presented more copy number alterations and a favorable prognosis.
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Hisham
authors.initials: H
authors.lastname: Abou-Taleb
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Murakami
authors.affiliation: Department of Obstetrics and Gynecology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Nakai
authors.affiliation: Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Higasa
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Amano
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Abiko
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshioka
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Hamanishi
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Koshiyama
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Baba
authors.affiliation: Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.affiliation: Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.affiliation: Department of Obstetrics and Gynecology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mandai
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000378:metabolism; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins; D059472:Exome / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D014157:Transcription Factors
keywords: SWI/SNF complex; clear cell carcinoma; copy number variation; ovarian cancer