Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions

Background Colorectal cancer is the second leading cause of cancer death in the United States, with over 50,000 deaths estimated in 2014. Molecular profiling for somatic mutations that predict absence of response to anti-EGFR therapy has become standard practice in the treatment of metastatic colore...

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Published in:Genome biology Vol. 15; no. 8; p. 454
Main Authors: Brannon, A Rose, Vakiani, Efsevia, Sylvester, Brooke E, Scott, Sasinya N, McDermott, Gregory, Shah, Ronak H, Kania, Krishan, Viale, Agnes, Oschwald, Dayna M, Vacic, Vladimir, Emde, Anne-Katrin, Cercek, Andrea, Yaeger, Rona, Kemeny, Nancy E, Saltz, Leonard B, Shia, Jinru, D’Angelica, Michael I, Weiser, Martin R, Solit, David B, Berger, Michael F
Format: Journal Article
Language:English
Published: London BioMed Central 28.08.2014
Subjects:
Adult
Aged
Aged, 80 and over
Alcohol Oxidoreductases - genetics
Animal Genetics and Genomics
Bioinformatics
Biomedical and Life Sciences
colorectal neoplasms
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
death
Evolutionary Biology
Female
genes
Genome, Human
Genomics of cancer progression and heterogeneity
GTP Phosphohydrolases - genetics
HEK293 Cells
high-throughput nucleotide sequencing
High-Throughput Nucleotide Sequencing - methods
Human Genetics
Humans
Life Sciences
Male
Membrane Proteins - genetics
metastasis
Microbial Genetics and Genomics
Middle Aged
Neoplasm Metastasis
patients
Plant Genetics and Genomics
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins B-raf - genetics
Proto-Oncogene Proteins p21(ras)
ras Proteins - genetics
Sequence Analysis, DNA - methods
somatic mutation
therapeutics
BRAF Mutation
Formalin Fixed Paraffin Embed
Metastatic Tissue
NRAS Mutation
Whole Genome Sequencing
ISSN:1474-760X, 1465-6906, 1474-760X, 1465-6914
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Summary:Background Colorectal cancer is the second leading cause of cancer death in the United States, with over 50,000 deaths estimated in 2014. Molecular profiling for somatic mutations that predict absence of response to anti-EGFR therapy has become standard practice in the treatment of metastatic colorectal cancer; however, the quantity and type of tissue available for testing is frequently limited. Further, the degree to which the primary tumor is a faithful representation of metastatic disease has been questioned. As next-generation sequencing technology becomes more widely available for clinical use and additional molecularly targeted agents are considered as treatment options in colorectal cancer, it is important to characterize the extent of tumor heterogeneity between primary and metastatic tumors. Results We performed deep coverage, targeted next-generation sequencing of 230 key cancer-associated genes for 69 matched primary and metastatic tumors and normal tissue. Mutation profiles were 100% concordant for KRAS , NRAS , and BRAF , and were highly concordant for recurrent alterations in colorectal cancer. Additionally, whole genome sequencing of four patient trios did not reveal any additional site-specific targetable alterations. Conclusions Colorectal cancer primary tumors and metastases exhibit high genomic concordance. As current clinical practices in colorectal cancer revolve around KRAS , NRAS , and BRAF mutation status, diagnostic sequencing of either primary or metastatic tissue as available is acceptable for most patients. Additionally, consistency between targeted sequencing and whole genome sequencing results suggests that targeted sequencing may be a suitable strategy for clinical diagnostic applications.
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ISSN:1474-760X
1465-6906
1474-760X
1465-6914
DOI:10.1186/s13059-014-0454-7