Oncotarget

Research Papers:

Genomic landscape of endometrial stromal sarcoma of uterus

Youn Jin Choi, Seung-Hyun Jung, Min Sung Kim, In-Pyo Baek, Jae-Keun Rhee, Sung Hak Lee, Soo Young Hur, Tae-Min Kim, Yeun-Jun Chung _ and Sug Hyung Lee

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Oncotarget. 2015; 6:33319-33328. https://doi.org/10.18632/oncotarget.5384

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Abstract

Youn Jin Choi1,* Seung-Hyun Jung2,3,* Min Sung Kim1, In-Pyo Baek2,3, Jae-Keun Rhee4, Sung Hak Lee5, Soo Young Hur7, Tae-Min Kim4, Yeun-Jun Chung2,3,6, Sug Hyung Lee1,2

1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea

2Department of Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea

3Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea

4Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea

5Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea

6Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea

7Department of Obstetrics/Gynecology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Yeun-Jun Chung, e-mail: yejun@catholic.ac.kr

Sug Hyung Lee, e-mail: suhulee@catholic.ac.kr

Keywords: endometrial stromal sarcoma, mutation, genome, whole exome, copy number

Received: July 07, 2015     Accepted: September 18, 2015     Published: September 30, 2015

ABSTRACT

Although recurrent gene fusions such as JAZF1-JJAZ1 are considered driver events for endometrial stromal sarcoma (ESS) development, other genomic alterations remain largely unknown. In this study, we performed whole-exome sequencing, transcriptome sequencing and copy number profiling for five ESSs (three low-grade ESS (LG-ESS) and two undifferentiated uterine sarcomas (UUSs)). All three LG-ESSs exhibited either one of JAZF1-SUZ12, JAZF1-PHF1 and MEAF6-PHF1 fusions, whereas the two UUSs did not. All ESSs except one LG-ESS exhibited copy number alterations (CNAs), many of which encompassed cancer-related genes. In UUSs, five CNAs encompassing cancer-related genes (EZR, CDH1, RB1, TP53 and PRKAR1A) accompanied their expressional changes, suggesting that they might stimulate UUS development. We found 81 non-silent mutations (35 from LG-ESSs and 46 from UUSs) that included 15 putative cancer genes catalogued in cancer-related databases, including PPARG and IRF4 mutations. However, they were non-recurrent and did not include any well-known mutations, indicating that point mutations may not be a major driver for ESS development. Our data show that gene fusions and CNAs are the principal drivers for LG-ESS and USS, respectively, but both may require additional genomic alterations including point mutations. These differences may explain the different biologic behaviors between LG-ESS and UUS. Our findings suggest that ESS development requires point mutations and CNAs as well as the gene fusions.


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