Patterns of somatic alterations between matched primary and metastatic colorectal tumors characterized by whole-genome sequencing - PubMed (original) (raw)
. 2014 Oct;104(4):234-41.
doi: 10.1016/j.ygeno.2014.07.012. Epub 2014 Jul 25.
Yong Beom Cho 2, Kai Wang 3, Donghui Huang 4, Hye Kyung Hong 5, Yoon-La Choi 6, Young Hyeh Ko 7, Do-Hyun Nam 8, Juyoun Jin 9, Heekyoung Yang 10, Julio Fernandez 11, Shibing Deng 12, Paul A Rejto 13, Woo Yong Lee 14, Mao Mao 15
Affiliations
- PMID: 25066378
- DOI: 10.1016/j.ygeno.2014.07.012
Free article
Patterns of somatic alterations between matched primary and metastatic colorectal tumors characterized by whole-genome sequencing
Tao Xie et al. Genomics. 2014 Oct.
Free article
Abstract
Colorectal cancer (CRC) patients have poor prognosis after formation of distant metastasis. Understanding the molecular mechanisms by which genetic changes facilitate metastasis is critical for the development of targeted therapeutic strategies aimed at controlling disease progression while minimizing toxic side effects. A comprehensive portrait of somatic alterations in CRC and the changes between primary and metastatic tumors has yet to be developed. We performed whole genome sequencing of two primary CRC tumors and their matched liver metastases. By comparing to matched germline DNA, we catalogued somatic alterations at multiple scales, including single nucleotide variations, small insertions and deletions, copy number aberrations and structural variations in both the primary and matched metastasis. We found that the majority of these somatic alterations are present in both sites. Despite the overall similarity, several de novo alterations in the metastases were predicted to be deleterious, in genes including FBXW7, DCLK1 and FAT2, which might contribute to the initiation and progression of distant metastasis. Through careful examination of the mutation prevalence among tumor cells at each site, we also proposed distinct clonal evolution patterns between primary and metastatic tumors in the two cases. These results suggest that somatic alterations may play an important role in driving the development of colorectal cancer metastasis and present challenges and opportunities when considering the choice of treatment.
Keywords: Colorectal cancer; Metastasis; Somatic alteration; Whole genome sequencing.
Copyright © 2014 Elsevier Inc. All rights reserved.
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