JCO:结直肠癌原发灶与转移灶的基因表型存在差异
2012-06-25 吴君德 王迈 MedSci原创
6月4日在线发表于J Clin Oncol的一项比较结直肠癌(CRC)原发灶与转移灶、转移灶之间基因突变情况的研究显示,TP53突变在转移灶中更为常见(53.1%对30.3%),而BRAF突变则在原发肿瘤中更多。 比较基因组杂交(CGH)数据显示,造成原发肿瘤与转移灶突变以及基因拷贝数分布差异的原因,可能是多个不同的CRC原发病灶或治疗相关效应。 原始文献: Va
6月4日在线发表于J Clin Oncol的一项比较结直肠癌(CRC)原发灶与转移灶、转移灶之间基因突变情况的研究显示,TP53突变在转移灶中更为常见(53.1%对30.3%),而BRAF突变则在原发肿瘤中更多。
比较基因组杂交(CGH)数据显示,造成原发肿瘤与转移灶突变以及基因拷贝数分布差异的原因,可能是多个不同的CRC原发病灶或治疗相关效应。
原始文献:
Vakiani E, Janakiraman M, Shen R, et al.Comparative Genomic Analysis of Primary Versus Metastatic Colorectal Carcinomas.J Clin Oncol. 2012 Jun 4.
PURPOSE To compare the mutational and copy number profiles of primary and metastatic colorectal carcinomas (CRCs) using both unpaired and paired samples derived from primary and metastatic disease sites. PATIENTS AND METHODSWe performed a multiplatform genomic analysis of 736 fresh frozen CRC tumors from 613 patients. The cohort included 84 patients in whom tumor tissue from both primary and metastatic sites was available and 31 patients with pairs of metastases. Tumors were analyzed for mutations in the KRAS, NRAS, BRAF, PIK3CA, and TP53 genes, with discordant results between paired samples further investigated by analyzing formalin-fixed, paraffin-embedded tissue and/or by 454 sequencing. Copy number aberrations in primary tumors and matched metastases were analyzed by comparative genomic hybridization (CGH).ResultsTP53 mutations were more frequent in metastatic versus primary tumors (53.1% v 30.3%, respectively; P < .001), whereas BRAF mutations were significantly less frequent (1.9% v 7.7%, respectively; P = .01). The mutational status of the matched pairs was highly concordant (> 90% concordance for all five genes). Clonality analysis of array CGH data suggested that multiple CRC primary tumors or treatment-associated effects were likely etiologies for mutational and/or copy number profile differences between primary tumors and metastases. CONCLUSIONFor determining RAS, BRAF, and PIK3CA mutational status, genotyping of the primary CRC is sufficient for most patients. Biopsy of a metastatic site should be considered in patients with a history of multiple primary carcinomas and in the case of TP53 for patients who have undergone interval treatment with radiation or cytotoxic chemotherapies.
作者:吴君德 王迈
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