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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Veröffentlicht in:	Genome biology Jg. 15; H. 8; S. 454
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	London BioMed Central 28.08.2014
Schlagworte:	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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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1474-760X 1465-6906 1474-760X 1465-6914
DOI:	10.1186/s13059-014-0454-7