High-depth sequencing of over 750 genes supports linear progression of primary tumors and metastases in most patients with liver-limited metastatic ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Iain Beehuat Tan, Simeen Malik, Kalpana Ramnarayanan, John R McPherson, Dan Liang Ho, Yuka Suzuki, Sarah Boonhsui Ng, Su Yan, Kiat Hon Lim, Dennis Koh, Chew Min Hoe, Chung Yip Chan, Rachel Ten, Brian KP Goh, Alexander YF Chung, Joanna Tan, Cheryl Xueli Chan, Su Ting Tay, Lezhava Alexander, Niranjan Nagarajan, Axel M Hillmer, Choon Leong Tang, Clarinda Chua, Bin Tean Teh, Steve Rozen, Patrick Tan

ABSTRACT

BACKGROUND: Colorectal cancer with metastases limited to the liver (liver-limited mCRC) is a distinct clinical subset characterized by possible cure with surgery. We performed high-depth sequencing of over 750 cancer-associated genes and copy number profiling in matched primary, metastasis and normal tissues to characterize genomic progression in 18 patients with liver-limited mCRC. RESULTS: High depth Illumina sequencing and use of three different variant callers enable comprehensive and accurate identification of somatic variants down to 2.5% variant allele frequency. We identify a median of 11 somatic single nucleotide variants (SNVs) per tumor. Across patients, a median of 79.3% of somatic SNVs present in the primary are present in the metastasis and 81.7% of all alterations present in the metastasis are present in the primary. Private alterations are found at lower allele frequencies; a different mutational signature characterized shared and private variants, suggesting distinct mutational processes. Using B-allele frequencies of heterozygous germline SNPs and copy number profiling, we find that broad regions of allelic imbalance and focal copy number changes, respectively, are generally shared between the primary tumor and metastasis. CONCLUSIONS: Our analyses point to high genomic concordance of primary tumor and metastasis, with a thick common trunk and smaller genomic branches in general support of the linear progression model in most patients with liver-limited mCRC. More extensive studies are warranted to further characterize genomic progression in this important clinical population. More... »

PAGES

32

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13059-015-0589-1

DOI

http://dx.doi.org/10.1186/s13059-015-0589-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1015434531

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25808843


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