Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers

Ji Hyun Lee, Xing Ming Zhao, Ina Yoon, Jin Young Lee, Nam Hoon Kwon, Yin Ying Wang, Kyung Min Lee, Min Joo Lee, Jisun Kim, Hyeong Gon Moon, Yongho In, Jin Kao Hao, Kyung Mii Park, Dong Young Noh, Wonshik Han, Sunghoon Kim

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Despite the explosion in the numbers of cancer genomic studies, metastasis is still the major cause of cancer mortality. In breast cancer, approximately one-fifth of metastatic patients survive 5 years. Therefore, detecting the patients at a high risk of developing distant metastasis at first diagnosis is critical for effective treatment strategy. We hereby present a novel systems biology approach to identify driver mutations escalating the risk of metastasis based on both exome and RNA sequencing of our collected 78 normal-paired breast cancers. Unlike driver mutations occurring commonly in cancers as reported in the literature, the mutations detected here are relatively rare mutations occurring in less than half metastatic samples. By supposing that the driver mutations should affect the metastasis gene signatures, we develop a novel computational pipeline to identify the driver mutations that affect transcription factors regulating metastasis gene signatures. We identify driver mutations in ADPGK, NUP93, PCGF6, PKP2 and SLC22A5, which are verified to enhance cancer cell migration and prompt metastasis with in vitro experiments. The discovered somatic mutations may be helpful for identifying patients who are likely to develop distant metastasis.

Original languageEnglish
Article number16025
JournalCell Discovery
Volume2
DOIs
Publication statusPublished - 2016 Aug 30

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers'. Together they form a unique fingerprint.

  • Cite this

    Lee, J. H., Zhao, X. M., Yoon, I., Lee, J. Y., Kwon, N. H., Wang, Y. Y., Lee, K. M., Lee, M. J., Kim, J., Moon, H. G., In, Y., Hao, J. K., Park, K. M., Noh, D. Y., Han, W., & Kim, S. (2016). Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers. Cell Discovery, 2, [16025]. https://doi.org/10.1038/celldisc.2016.25