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

Genome Biol 2014 Aug 28;15(8):454. Epub 2014 Aug 28.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-014-0454-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189196PMC
August 2014

Publication Analysis

Top Keywords

colorectal cancer
28
primary metastatic
16
kras nras
8
high genomic
8
nras braf
8
genomic concordance
8
targeted sequencing
8
genome sequencing
8
next-generation sequencing
8
matched primary
8
cancer
8
metastatic colorectal
8
sequencing
7
colorectal
7
metastatic
6
primary
6
metastatic tumors
4
tumors normal
4
genes matched
4
cancer-associated genes
4

Altmetric Statistics

Similar Publications