KRAS, NRAS, PIK3CA Exon 20, and BRAF Genotypes in Synchronous and Metachronous Primary Colorectal Cancers Diagnostic and Therapeutic Implications
KRAS, NRAS, PIK3CA Exon 20, and BRAF Genotypes in Synchronous and Metachronous Primary Colorectal Cancers Diagnostic and Therapeutic Implications
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DOI：
10.1016/j.jmoldx.2011.03.002
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发表时间：
2011-07-01
影响因子：
4.1
通讯作者：
Roecken, Christoph
中科院分区：
文献类型：
--
作者：
Balschun, Katharina;Haag, Jochen;Roecken, Christoph
晚期结直肠癌的靶向治疗需要KRAS基因分型。由于我们对诊断和治疗结果感兴趣，我们研究了同步和异时原发性CRC中的KRAS、NRAS、PIK 3CA外显子20和BRAF基因型;此外，我们还研究了其可能的转移。我们研究了21例患者的43个同时性和2个异时性腺癌的结直肠（n = 20）和胃（n = 1）。5例患者有肝转移，1例有远处淋巴结转移。从显微切割的肿瘤组织中提取基因组DNA。通过桑格测序和焦磷酸测序分析DNA。对57例不同的肿瘤性病变进行了基因分型，显示18例（31.6%）KRAS、2例（3.5%）NRAS和7例（12.3%）BRAF突变，分布于10例（47.6%）、1例（4.8%）和5例（23.8%）患者中。仅7例（35%）患者的所有同步原发性CRC基因型相同;其余患者的基因型不同，组合不同。有趣的是，一名患者具有未知的KRAS基因型（c.37_39dupGGC）。6例患者的13个原发癌有远处转移。在这些患者中的3例中，转移瘤仅与一种原发性肿瘤共享基因型，因为其他原发性肿瘤具有另一种基因型。同一患者的同步和异时原发性CRC具有不同的KRAS、NRAS和BRAF基因型。当这些患者发生转移时，基因型具有诊断和治疗意义，应根据同时或异时远处转移确定。（J Mol Diagn 2011，13：436-445; DOI：10.1016/j.jmoldx.2011.03.002）
Targeted therapy of advanced colorectal carcinoma (CRC) necessitates KRAS genotyping. Because we were interested in diagnostic and therapeutic consequences, we studied the KRAS, NRAS, PIK3CA exon 20, and BRAF genotypes in synchronous and metachronous primary CRCs; in addition, we studied their available metastases. We studied 21 patients with 43 synchronous and 2 metachronous adenocarcinomas of the colorectum (n = 20) and stomach (n = 1). Five patients had liver metastases and one had a distant lymph node metastasis. Genomic DNA was extracted from microdissected tumor tissue. The DNA was analyzed by Sanger sequencing and pyrosequencing. Fifty-seven different neoplastic lesions were genotyped, showing 18 (31.6%) KRAS, 2 (3.5%) NRAS, and 7 (12.3%) BRAF mutations, distributed among 10 (47.6%), 1 (4.8%), and 5 (23.8%) of the patients. An identical genotype of all synchronous primary CRCs was found only in 7 (35%) of the patients; the remainder had dissimilar genotypes in various combinations. Interestingly, a single patient had an unknown KRAS genotype (c.37_39dupGGC). Six patients with 13 primary carcinomas had distant metastases. In three of these patients, the metastasis shared the genotype only with one of the primary tumors, because the other primary tumors had another genotype. Synchronous and metachronous primary CRCs of the same patient have variable KRAS, NRAS, and BRAF genotypes. When metastases occur in these patients, the genotype has diagnostic and therapeutic implications and should be determined from the simultaneous or metachronous distant metastases. (J Mol Diagn 2011, 13:436-445; DOI: 10.1016/j.jmoldx.2011.03.002)