Research Papers:

Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas

Hio Chung Kang _, Hong Kwan Kim, Sharon Lee, Pedro Mendez, James Wansoo Kim, Gavitt Woodard, Jun-Hee Yoon, Kuang-Yu Jen, Li Tai Fang, Kirk Jones, David M. Jablons and Il-Jin Kim

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:8321-8331. https://doi.org/10.18632/oncotarget.7032

Metrics: PDF 1905 views  |   HTML 2816 views  |   ?  


Hio Chung Kang1,2,*, Hong Kwan Kim1,3,*, Sharon Lee4, Pedro Mendez1, James Wansoo Kim4, Gavitt Woodard1, Jun-Hee Yoon1, Kuang-Yu Jen5, Li Tai Fang1, Kirk Jones5, David M. Jablons1,2, Il-Jin Kim1,2

1Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA

2Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA

3Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

4CureSeq Inc, Brisbane, CA, USA

5Department of Pathology, University of California San Francisco, San Francisco, CA, USA

*These authors have contributed equally to this work

Correspondence to:

Il-Jin Kim, e-mail: [email protected]

David M. Jablons, e-mail: [email protected]

Keywords: malignant pleural mesothelioma, multiple primary cancer, genome-wide allelic loss, exome sequencing, SETDB1

Received: October 05, 2015     Accepted:     January 15, 2016     Published: January 27, 2016


Malignant pleural mesothelioma (MPM), a rare malignancy with a poor prognosis, is mainly caused by exposure to asbestos or other organic fibers, but the underlying genetic mechanism is not fully understood. Genetic alterations and causes for multiple primary cancer development including MPM are unknown. We used whole exome sequencing to identify somatic mutations in a patient with MPM and two additional primary cancers who had no evidence of venous, arterial, lymphovascular, or perineural invasion indicating dissemination of a primary lung cancer to the pleura. We found that the MPM had R282W, a key TP53 mutation, and genome-wide allelic loss or loss of heterozygosity, a distinct genomic alteration not previously described in MPM. We identified frequent inactivating SETDB1 mutations in this patient and in 68 additional MPM patients (mutation frequency: 10%, 7/69) by targeted deep sequencing. Our observations suggest the possibility of a new genetic mechanism in the development of either MPM or multiple primary cancers. The frequent SETDB1 inactivating mutations suggest there could be new diagnostic or therapeutic options for MPM.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 7032