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.
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DOI：
10.1186/s13059-014-0454-7
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发表时间：
2014-08-28
期刊：
影响因子：
12.3
通讯作者：
Berger MF
中科院分区：
文献类型：
--
作者：
Brannon AR;Vakiani E;Sylvester BE;Scott SN;McDermott G;Shah RH;Kania K;Viale A;Oschwald DM;Vacic V;Emde AK;Cercek A;Yaeger R;Kemeny NE;Saltz LB;Shia J;D'Angelica MI;Weiser MR;Solit DB;Berger MF
结直肠癌是美国癌症死亡的第二大原因，2014年估计有超过50，000人死亡。预测抗EGFR治疗无应答的体细胞突变的分子谱分析已成为转移性结直肠癌治疗的标准实践;然而，可用于检测的组织数量和类型通常有限。此外，原发性肿瘤在多大程度上是转移性疾病的忠实代表一直受到质疑。随着下一代测序技术越来越广泛地用于临床，以及其他分子靶向药物被认为是结直肠癌的治疗选择，重要的是要表征原发性和转移性肿瘤之间的肿瘤异质性程度。我们对69个匹配的原发性和转移性肿瘤以及正常组织的230个关键癌症相关基因进行了深度覆盖，有针对性的下一代测序。KRAS、NRAS和BRAF的突变谱是100%一致的，并且与结直肠癌的复发性改变高度一致。此外，四个患者三人组的全基因组测序没有显示任何额外的位点特异性靶向改变。结直肠癌原发肿瘤和转移瘤表现出高基因组一致性。由于结直肠癌的当前临床实践围绕KRAS、NRAS和BRAF突变状态，因此大多数患者可以接受可用的原发性或转移性组织的诊断测序。此外，靶向测序和全基因组测序结果之间的一致性表明，靶向测序可能是临床诊断应用的合适策略。本文的在线版本（doi：10.1186/s13059-014-0454-7）包含补充材料，可供授权用户使用。
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. 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. 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. The online version of this article (doi:10.1186/s13059-014-0454-7) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.0712345105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Jones, Sian;Chen, Wei-dong;Markowitz, Sanford D.
通讯作者：
Markowitz, Sanford D.
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA
影响因子：
11.5
作者：
Vermaat, Joost S.;Nijman, Isaac J.;Voest, Emile E.
通讯作者：
Voest, Emile E.
影响因子：
45.3
作者：
Vakiani, Efsevia;Janakiraman, Manickam;Solit, David B.
通讯作者：
Solit, David B.
影响因子：
5.8
作者：
Saunders, Christopher T.;Wong, Wendy S. W.;Cheetham, R. Keira
通讯作者：
Cheetham, R. Keira