DNA sequence profiles of the colorectal cancer critical gene set KRAS-BRAF-PIK3CA-PTEN-TP53 related to age at disease onset.
DNA sequence profiles of the colorectal cancer critical gene set KRAS-BRAF-PIK3CA-PTEN-TP53 related to age at disease onset.
复制标题
结直肠癌关键基因组 KRAS-BRAF-PIK3CA-PTEN-TP53 的 DNA 序列图谱与发病年龄相关。
DOI：
10.1371/journal.pone.0013978
复制
发表时间：
2010-11-12
期刊：
影响因子：
3.7
通讯作者：
Lothe RA
中科院分区：
文献类型：
--
作者：
Berg M;Danielsen SA;Ahlquist T;Merok MA;Ågesen TH;Vatn MH;Mala T;Sjo OH;Bakka A;Moberg I;Fetveit T;Mathisen Ø;Husby A;Sandvik O;Nesbakken A;Thiis-Evensen E;Lothe RA
结直肠癌（CRC）的发病率随着年龄的增长而增加，并且发病早表明该疾病的遗传倾向的可能性增加。肿瘤发展与患者年龄相关的体细胞遗传学仍然大多未知。我们检查了与诊断时年龄相关的五个已知癌症关键基因的突变状态，并将无已知 CRC 综合征的年轻患者的肿瘤基因组复杂性与老年患者的肿瘤基因组复杂性进行了比较。在 181 名 CRC 患者中，按微卫星不稳定状态分层，在 KRAS (32%)、BRAF (16%)、PIK3CA (4%)、PTEN (14%) 和 TP53 (51%) 中发现 DNA 序列变化。在 50 岁以下的患者中 (n = 45)，未观察到 PIK3CA 突变，而 TP53 突变比年龄较大的患者更频繁。最年轻患者的肿瘤总基因突变指数最低。相比之下，以拷贝数畸变评估的基因组复杂性在最年轻患者的肿瘤中最高。来自年轻患者（<50 岁）和老年患者（>70 岁）的相当数量的肿瘤对四种预测基因标记物 (KRAS-BRAF-PIK3CA-PTEN) 呈四阴性；然而，16% 的年轻患者仅存在 PTEN/PIK3CA 肿瘤突变，而只有 1% 的老年患者仅存在 PTEN/PIK3CA 肿瘤突变。这意味着预测 EGFR 治疗反应的突变检测可能仅限于老年（>70 岁）患者的 KRAS 和 BRAF。在年轻和老年患者的肿瘤中发现的明显遗传差异（已知的临床和病理变量具有可比性）表明，年轻患者与老年患者相比，具有不同的 CRC 发展遗传风险特征。
The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients.
登录
查看更多内容
影响因子：
37.3
作者：
Berg M;Agesen TH;Thiis-Evensen E;INFAC-study group;Merok MA;Teixeira MR;Vatn MH;Nesbakken A;Skotheim RI;Lothe RA
通讯作者：
Lothe RA
癌症中躯体突变的目录（宇宙）。
影响因子：
--
作者：
Forbes, S A;Bhamra, G;Bamford, S;Dawson, E;Kok, C;Clements, J;Menzies, A;Teague, J W;Futreal, P A;Stratton, M R
通讯作者：
Stratton, M R
影响因子：
3.3
作者：
Frizis, H;Papadopoulos, A;Hatzitheoharis, G
通讯作者：
Hatzitheoharis, G
影响因子：
3.9
作者：
Gonzalez, EC;Roetzheim, RG;Campbell, R
通讯作者：
Campbell, R
影响因子：
158.5
作者：
Gryfe, R;Kim, H;Gallinger, S
通讯作者：
Gallinger, S