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Sci Rep. 2019 Mar 14;9(1):4542. doi: 10.1038/s41598-019-41098-0.

Intratumor heterogeneity inferred from targeted deep sequencing as a prognostic indicator.

Author information

1
Department of Colorectal Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.
2
Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
3
New York Genome Center, New York, NY, USA.
4
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
5
Department of Health Sciences and Technology, Samsung Advanced Institute of Science and Health Technology, Sungkyunkwan University, Seoul, Korea.
6
Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
7
Samsung Genome Institute, Samsung Medical Center, Seoul, Korea. jegun.joung@samsung.com.
8
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. hc111.kim@samsung.com.
9
Samsung Genome Institute, Samsung Medical Center, Seoul, Korea. woongyang.park@samsung.com.
10
Department of Health Sciences and Technology, Samsung Advanced Institute of Science and Health Technology, Sungkyunkwan University, Seoul, Korea. woongyang.park@samsung.com.
11
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea. woongyang.park@samsung.com.
12
GENINUS Inc., Seoul, Korea. woongyang.park@samsung.com.

Abstract

Tumor genetic heterogeneity may underlie poor clinical outcomes because diverse subclones could be comprised of metastatic and drug resistant cells. Targeted deep sequencing has been used widely as a diagnostic tool to identify actionable mutations in cancer patients. In this study, we evaluated the clinical utility of estimating tumor heterogeneity using targeted panel sequencing data. We investigated the prognostic impact of a tumor heterogeneity (TH) index on clinical outcomes, using mutational profiles from targeted deep sequencing data acquired from 1,352 patients across 8 cancer types. The TH index tended to be increased in high pathological stage disease in several cancer types, indicating clonal expansion of cancer cells as tumor progression proceeds. In colorectal cancer patients, TH index values also correlated significantly with clinical prognosis. Integration of the TH index with genomic and clinical features could improve the power of risk prediction for clinical outcomes. In conclusion, deep sequencing to determine the TH index could serve as a promising prognostic indicator in cancer patients.

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