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Tumor heterogeneity predicts metastatic potential in colorectal cancer

Title
Tumor heterogeneity predicts metastatic potential in colorectal cancer
Authors
Joung J.-G.Oh B.Y.Hong H.K.Al-Khalidi H.Al-Alem F.Lee H.-O.Bae J.S.Kim J.Cha H.-U.Alotaibi M.Cho Y.B.Hassanain M.Park W.-Y.Lee W.Y.
Ewha Authors
오보영
SCOPUS Author ID
오보영scopus
Issue Date
2017
Journal Title
Clinical Cancer Research
ISSN
1078-0432JCR Link
Citation
Clinical Cancer Research vol. 23, no. 23, pp. 7209 - 7216
Publisher
American Association for Cancer Research Inc.
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Purpose: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer tumor samples to determine whether tumor heterogeneity can predict tumor metastasis. Experimental Design: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole-exome sequencing. Tumor clonality was estimated from single-nucleotide and copy-number variations. The correlation between clinical parameters of patients and clonal heterogeneity in liver metastasis was evaluated. Results: Tumor heterogeneity across colorectal cancer samples was highly variable; however, a high degree of tumor heterogeneity was associated with a worse disease-free survival. Highly heterogeneous primary colorectal cancer was correlated with a higher rate of liver metastasis. Recurrent somatic mutations in APC, TP53, and KRAS were frequently detected in highly heterogeneous colorectal cancer. The variant allele frequency of these mutations was high, while somatic mutations in other genes such as PIK3CA and NOTCH1 were low. The number and distribution of primary colorectal cancer subclones were preserved in metastatic tumors. Conclusions: Heterogeneity of primary colorectal cancer tumors can predict the potential for liver metastasis and thus, clinical outcome of patients. ©2017 AACR.
DOI
10.1158/1078-0432.CCR-17-0306
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의료원 > 의료원 > Journal papers
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