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, Il Jin Kim

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8321-8331
Number of pages11
JournalOncotarget
Volume7
Issue number7
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Keywords

  • Exome sequencing
  • Genome-wide allelic loss
  • Malignant pleural mesothelioma
  • Multiple primary cancer
  • SETDB1

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Kang, H. C., Kim, H. K., Lee, S., Mendez, P., Kim, J. W., Woodard, G., Yoon, J. H., Jen, K-Y., Fang, L. T., Jones, K., Jablons, D. M., & Kim, I. J. (2016). Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas. Oncotarget, 7(7), 8321-8331. https://doi.org/10.18632/oncotarget.7032