Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.
Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.
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DOI：
10.1054/bjoc.2001.1964
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发表时间：
2001-09-01
影响因子：
8.8
通讯作者：
Urosevic N
中科院分区：
文献类型：
--
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
研究人员邀请世界各地的研究人员提供有关Kirsten ras （Ki-ras）肿瘤基因型和结直肠癌患者预后的信息，以图表形式提供这些数据，以纳入一个名为RASCAL的合作数据库（the Kirsten ras in-colorectal-cancer collaborative group）。我们对2721例这样的患者的研究结果已经在任何一种常见癌症中首次提出，结果表明不同的基因突变对结果有不同的影响，即使突变发生在基因组的同一位点。为了探索Ki-ras突变在结直肠癌不同阶段的影响，更多的患者被招募到数据库中，当来自21个国家42个中心的4268名患者的信息被输入时，该数据库被重新分析。应用预先确定的排除标准后，对3439例患者的数据进行多变量分析。研究发现，在Kirsten ras的12个可能的密码子12和13突变中，只有8.6%的患者发现了一个密码子甘氨酸到缬氨酸的突变，对无衰竭生存（P = 0.004, HR 1.3）和总生存（P = 0.008, HR 1.29）有统计学意义的影响。该突变似乎对Dukes的C癌（无失败生存期，P = 0.008, HR 1.5；总生存期P = 0.02, HR 1.45）比Dukes的B癌（无失败生存期，P = 0.46, HR 1.12；总生存期P = 0.36, HR 1.15）的预后有更大的影响。Ki-ras突变可能发生在结肠和直肠癌前腺瘤的早期发展。然而，这项合作研究表明，密码子12甘氨酸到缬氨酸突变的存在不仅对癌症进展很重要，而且可能使晚期结直肠癌患者更易发生更具攻击性的生物学行为。©2001癌症研究运动http://www.bjcancer.com
Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes’ C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes’ B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com
影响因子：
158.5
作者：
VOGELSTEIN, B;FEARON, ER;BOS, JL
通讯作者：
BOS, JL
DOI：
10.1093/jnci/90.9.675
发表时间：
1998-05-06
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Andreyev, HJN;Norman, AR;Clarke, PA
通讯作者：
Clarke, PA
影响因子：
7.3
作者：
Al-Mulla, F;Milner-White, EJ;Birnie, GD
通讯作者：
Birnie, GD