Mutation status and prognostic values of KRAS, NRAS, BRAF and PIK3CA in 353 Chinese colorectal cancer patients

• Published in: Scientific reports 2018-04, Vol.8 (1), p.6076-11, Article 6076
• Main Authors: Guo, Fang, Gong, Hai, Zhao, Huanhuan, Chen, Jing, Zhang, Yiming, Zhang, Lihua, Shi, Xin, Zhang, Aifeng, Jin, Hui, Zhang, Jianqiong, He, Youji
• Format: Article
• Language: English
• Subjects: 38/23; 38/77; 631/67/1857; 631/67/2324; 692/4028; Colorectal cancer; Colorectal carcinoma; Humanities and Social Sciences; K-Ras protein; Metastases; multidisciplinary; Mutation; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-24306-1

Mutations in KRAS exon 2, BRAF and PIK3CA are commonly present in colorectal cancer (CRC) worldwide, but few data about RAS mutations outside KRAS exon 2 are available for Chinese CRCs. We, therefore, determined the mutation frequencies and prognostic values of KRAS exon 2, 3 and 4, NRAS exon 2 and 3, PIK3CA exon 9 and 20, and BRAF exon 15 by PCR and direct sequencing in 353 CRC patients from two Chinese clinical centers. KRAS exon 2, BRAF , PIK3CA mutations were identified in 42.2%, 4.5%, 12.3% of the cases, respectively. We found “rare mutations” in RAS genes in nearly 14% of CRCs-i.e., in almost a quarter (24.0%) of KRAS exon 2 wild type CRCs, including 2.3% in KRAS exon 3, 8.2% in KRAS exon 4 and 3.4% in NRAS . Stage I-III patients with PIK3CA or NRAS mutations developed more distant metastases (3-year risk in PIK3CA mutated and wild type patients: 23.3% vs 11.5%, P = 0.03; multivariate Hazard ratio (HR) = 3.129, P = 0.003; 3-year risk in NRAS mutated and wild type patients: 40.0% vs 12.2%, P = 0.012; multivariate HR = 5.152, P = 0.003). Our data emphasizes the importance of these novel molecular features in CRCs.