Gorukmez Orhan, Yakut Tahsin, Gorukmez Ozlem, Sag Sebnem Ozemri, Karkucak Mutlu, Kanat Ozkan
Medical Genetics Unit, Sevket Yilmaz Training and Research Hospital, Bursa, Turkey E-mail :
Asian Pac J Cancer Prev. 2016;17(3):1175-9. doi: 10.7314/apjcp.2016.17.3.1175.
The results of this study demonstrate the potential prognostic and predictive values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC). It has been proven that KRAS and BRAF mutations are predictive biomarkers for resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared the results with clinicopathological data. KRAS and BRAF mutations were identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of the positive patients, respectively. The KRAS mutation frequency was significantly higher in tumors located in the ascending colon (p=0.043). Thus, we found that approximately 1/3 of the patients with mCRC had KRAS mutations and the only clinicopathological factor related to this mutation was tumor location. Future studies with larger patient groups should yield more accurate data regarding the molecular mechanism of CRC and the association between KRAS and BRAF mutations and clinicopathological features.
本研究结果证明了KRAS和BRAF基因突变在结直肠癌（CRC）患者中的潜在预后和预测价值。已证实KRAS和BRAF突变是转移性结直肠癌（mCRC）患者抗表皮生长因子受体（EGFR）单克隆抗体治疗耐药的预测生物标志物。我们采用直接测序法检测了50例mCRC中KRAS（密码子12、13和61）和BRAF（密码子600）基因突变的分布情况，并将结果与临床病理数据进行比较。KRAS和BRAF突变分别在15例（30%）和1例（2%）患者中被检测到。在KRAS突变阳性患者中，密码子12、13和61的突变分别占73.3%（11/15）、20%（3/15）和6.67%（1/15）。升结肠癌中KRAS突变频率显著更高（p = 0.043）。因此，我们发现约1/3的mCRC患者存在KRAS突变，且与该突变相关的唯一临床病理因素是肿瘤位置。未来针对更大患者群体的研究应能提供关于CRC分子机制以及KRAS和BRAF突变与临床病理特征之间关联的更准确数据。
