Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma
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Hisham Abou-Taleb1,2, Ken Yamaguchi1, Noriomi Matsumura1, Ryusuke Murakami1, Hidekatsu Nakai3, Koichiro Higasa4, Yasuaki Amano1, Kaoru Abiko1, Yumiko Yoshioka1, Junzo Hamanishi1, Masafumi Koshiyama1, Tsukasa Baba1, Ryo Yamada4, Fumihiko Matsuda4, Ikuo Konishi1, Masaki Mandai3
1Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
2Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, Assiut, Egypt
3Department of Obstetrics and Gynecology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan
4Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Ken Yamaguchi, email: [email protected]
Keywords: clear cell carcinoma, ovarian cancer, SWI/SNF complex, copy number variation
Received: October 29, 2015 Accepted: June 01, 2016 Published: June 20, 2016
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.
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