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

Publication ,  Journal Article
Tan, IB; Malik, S; Ramnarayanan, K; McPherson, JR; Ho, DL; Suzuki, Y; Ng, SB; Yan, S; Lim, KH; Koh, D; Hoe, CM; Chan, CY; Ten, R; Goh, BK ...
Published in: Genome Biol
February 12, 2015

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.

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Published In

Genome Biol

DOI

EISSN

1474-760X

Publication Date

February 12, 2015

Volume

16

Issue

1

Start / End Page

32

Location

England

Related Subject Headings

  • Neoplasms, Multiple Primary
  • Mutation
  • Molecular Sequence Data
  • Liver Neoplasms
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Genome, Human
  • Genes, Neoplasm
  • Gene Frequency
  • Disease Progression
 

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Tan, I. B., Malik, S., Ramnarayanan, K., McPherson, J. R., Ho, D. L., Suzuki, Y., … Tan, P. (2015). High-depth sequencing of over 750 genes supports linear progression of primary tumors and metastases in most patients with liver-limited metastatic colorectal cancer. Genome Biol, 16(1), 32. https://doi.org/10.1186/s13059-015-0589-1
Tan, Iain Beehuat, Simeen Malik, Kalpana Ramnarayanan, John R. McPherson, Dan Liang Ho, Yuka Suzuki, Sarah Boonhsui Ng, et al. “High-depth sequencing of over 750 genes supports linear progression of primary tumors and metastases in most patients with liver-limited metastatic colorectal cancer.Genome Biol 16, no. 1 (February 12, 2015): 32. https://doi.org/10.1186/s13059-015-0589-1.
Tan, Iain Beehuat, et al. “High-depth sequencing of over 750 genes supports linear progression of primary tumors and metastases in most patients with liver-limited metastatic colorectal cancer.Genome Biol, vol. 16, no. 1, Feb. 2015, p. 32. Pubmed, doi:10.1186/s13059-015-0589-1.
Tan IB, Malik S, Ramnarayanan K, McPherson JR, Ho DL, Suzuki Y, Ng SB, Yan S, Lim KH, Koh D, Hoe CM, Chan CY, Ten R, Goh BK, Chung AY, Tan J, Chan CX, Tay ST, Alexander L, Nagarajan N, Hillmer AM, Tang CL, Chua C, Teh BT, Rozen S, Tan P. High-depth sequencing of over 750 genes supports linear progression of primary tumors and metastases in most patients with liver-limited metastatic colorectal cancer. Genome Biol. 2015 Feb 12;16(1):32.

Published In

Genome Biol

DOI

EISSN

1474-760X

Publication Date

February 12, 2015

Volume

16

Issue

1

Start / End Page

32

Location

England

Related Subject Headings

  • Neoplasms, Multiple Primary
  • Mutation
  • Molecular Sequence Data
  • Liver Neoplasms
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Genome, Human
  • Genes, Neoplasm
  • Gene Frequency
  • Disease Progression