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

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

Authors:	Brannon, A. R.; Vakiani, E.; Sylvester, B. E.; Scott, S. N.; McDermott, G.; Shah, R. H.; Kania, K.; Viale, A.; Oschwald, D. M.; Vacic, V.; Emde, A. K.; Cercek, A.; Yaeger, R.; Kemeny, N. E.; Saltz, L. B.; Shia, J. R.; D'Angelica, M. I.; Weiser, M. R.; Solit, D. B.; Berger, M. F.
Article Title:	Comparative sequencing analysis reveals high genomic concordance between matched primary and metastatic colorectal cancer lesions
Abstract:	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.
Keywords:	evolution; tumors; therapy; mutations; heterogeneity; acquired-resistance; benefit
Journal Title:	Genome Biology
Volume:	15
Issue:	8
ISSN:	1465-6906
Publisher:	Biomed Central Ltd
Date Published:	2014-08-28
Start Page:	454
Language:	English
ACCESSION:	WOS:000346604100029
DOI:	10.1186/s13059-014-0454-7
PROVIDER:	wos
PMCID:	PMC4189196
PUBMED:	25164765
Notes:	Article -- 454 -- Source: Wos