Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.
Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.
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DOI：
10.1186/s12967-016-1053-z
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发表时间：
2016-10-13
影响因子：
7.4
通讯作者：
Palmieri G
中科院分区：
文献类型：
--
作者：
Palomba G;Doneddu V;Cossu A;Paliogiannis P;Manca A;Casula M;Colombino M;Lanzillo A;Defraia E;Pazzola A;Sanna G;Putzu C;Ortu S;Scartozzi M;Ionta MT;Baldino G;Sarobba G;Capelli F;Sedda T;Virdis L;Barca M;Gramignano G;Budroni M;Tanda F;Palmieri G
EGFR基因下游癌基因的激活有助于结直肠肿瘤的发生，并决定了抗EGFR治疗的敏感性。本研究的目的是评估KRAS、BRAF、NRAS和PIK3CA突变在大量基因同质撒丁岛人群CRC患者中的预后价值。共有1284名经组织学证实诊断为结直肠癌（CRC）并表现为转移性疾病的撒丁岛患者被纳入研究。从福尔马林固定、石蜡包埋的结直肠癌患者原发肿瘤组织样本中分离基因组DNA，使用焦磷酸测序法筛选RAS和BRAF基因突变，使用自动DNA测序法筛选PIK3CA基因突变。总的来说，KRAS的突变率为35.6%，NRAS为4.1%，BRAF为2.1%。在现有的DNA样本中，114/796（14.3%）原发性crc被发现携带PIK3CA基因突变。在所有四种基因分析的患者亚组中，在大约一半（378/796;47.5%）的CRC病例中发现至少一种基因的致病突变。研究发现，突变的BRAF基因在转移性疾病进展时间（从发现原发性结直肠癌到诊断首次远处转移，p = 0.009）、部分生存期（从诊断晚期疾病到死亡时间或最后一次对照，p = 0.006）或总生存期（p < 0.001）中均稳定地发挥着负面预后因素的作用。KRAS、NRAS和PIK3CA基因突变或RAS联合突变（全部RAS）对预后无显著影响。我们的研究在以人群为基础的大量CRC患者中定义了主要激活癌基因的患病率和预后作用。本文的在线版本（doi:10.1186/s12967-016-1053-z）包含补充材料，可供授权用户使用。
Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population. A total of 1284 Sardinian patients with histologically-proven diagnosis of colorectal carcinoma (CRC) and presenting with metastatic disease were included into the study. Genomic DNA was isolated from formalin-fixed, paraffin-embedded primary tumour tissue samples of CRC patients and screened for mutations in RAS and BRAF genes, using pyrosequencing assays, and in PIK3CA gene, using automated DNA sequencing assays. Overall, mutation rates were 35.6 % for KRAS, 4.1 % for NRAS, and 2.1 % for BRAF. Among available DNA samples, 114/796 (14.3 %) primary CRCs were found to carry a mutation in the PIK3CA gene. In this subset of patients analysed in all four genes, a pathogenetic mutation of at least one gene was discovered in about half (378/796; 47.5 %) of CRC cases. A mutated BRAF gene was found to steadily act as a negative prognostic factor for either time to progression as metastatic disease (from detection of primary CRC to diagnosis of first distant metastasis; p = 0.009) or partial survival (from diagnosis of advanced disease to the time of death or last control; p = 0.006) or overall survival (p < 0.001). No significant impact on prognosis was observed for mutated KRAS, NRAS, and PIK3CA genes or combined RAS mutations (all RAS). Our study defines both prevalence and prognostic role of main activated oncogenes in a population-based large collection of CRC patients. The online version of this article (doi:10.1186/s12967-016-1053-z) contains supplementary material, which is available to authorized users.
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BRAF V600E 突变和 KRAS 密码子 13 突变预测中国结直肠癌患者生存率较差
影响因子：
3.8
作者：
Chen J;Guo F;Shi X;Zhang L;Zhang A;Jin H;He Y
通讯作者：
He Y
影响因子：
11.5
作者：
Baldus, Stephan E.;Schaefer, Karl-L.;Gabbert, Helmut E.
通讯作者：
Gabbert, Helmut E.
影响因子：
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作者：
Bronte G;Silvestris N;Castiglia M;Galvano A;Passiglia F;Sortino G;Cicero G;Rolfo C;Peeters M;Bazan V;Fanale D;Giordano A;Russo A
通讯作者：
Russo A
影响因子：
8.8
作者：
Andreyev HJ;Norman AR;Cunningham D;Oates J;Dix BR;Iacopetta BJ;Young J;Walsh T;Ward R;Hawkins N;Beranek M;Jandik P;Benamouzig R;Jullian E;Laurent-Puig P;Olschwang S;Muller O;Hoffmann I;Rabes HM;Zietz C;Troungos C;Valavanis C;Yuen ST;Ho JW;Croke CT;O'Donoghue DP;Giaretti W;Rapallo A;Russo A;Bazan V;Tanaka M;Omura K;Azuma T;Ohkusa T;Fujimori T;Ono Y;Pauly M;Faber C;Glaesener R;de Goeij AF;Arends JW;Andersen SN;Lövig T;Breivik J;Gaudernack G;Clausen OP;De Angelis PD;Meling GI;Rognum TO;Smith R;Goh HS;Font A;Rosell R;Sun XF;Zhang H;Benhattar J;Losi L;Lee JQ;Wang ST;Clarke PA;Bell S;Quirke P;Bubb VJ;Piris J;Cruickshank NR;Morton D;Fox JC;Al-Mulla F;Lees N;Hall CN;Snary D;Wilkinson K;Dillon D;Costa J;Pricolo VE;Finkelstein SD;Thebo JS;Senagore AJ;Halter SA;Wadler S;Malik S;Krtolica K;Urosevic N
通讯作者：
Urosevic N
影响因子：
50.5
作者：
Bazan, V.;Agnese, V.;Russo, Antonio
通讯作者：
Russo, Antonio