NRAS and BRAF mutations in melanoma turnours in re ation to clinical characteristics:: a study based on mutation screening by pyrosequencing
NRAS and BRAF mutations in melanoma turnours in re ation to clinical characteristics:: a study based on mutation screening by pyrosequencing
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DOI：
10.1097/01.cmr.0000232300.22032.86
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发表时间：
2006-12-01
影响因子：
2.2
通讯作者：
Lundeberg, Joakim
中科院分区：
文献类型：
--
作者：
Edlundh-Rose, Esther;Egyhazi, Suzanne;Lundeberg, Joakim
我们之前已经证明了在黑色素瘤活检中使用焦磷酸测序来研究NRAS[神经母细胞瘤RAS病毒（v-ras）癌基因同源]突变。在这里，我们将分析扩展到BRAF (V-raf小鼠肉瘤病毒癌基因同源物1311)，ras -raf -丝裂原激活蛋白激酶（MAPK）信号通路的另一个成员，并分析了219例患者的294例黑色素瘤。156例（53%）肿瘤中发现BRAF外显子11和15突变，86例（29%）肿瘤中发现NRAS外显子2突变。总体而言，294个肿瘤中有242个发现了NRAS或BRAF突变；（82%），并且在除两种情况（0.7%）外的所有情况下都是互斥的。在57例病例中分析了多发转移，除3例外，其余病例的突变相同，表明BRAF和NRAS突变发生在转移前。在BRAF突变的肿瘤中，与先前存在痣的相关性显著升高（P=0.014）。此外，BRAF突变的肿瘤表现出更频繁的中度至明显淋巴细胞浸润（P=0.013）。与BRAF突变相比，NRAS突变与更高的Clark侵袭水平相关（P=0.022）。NRAS突变患者的诊断年龄明显高于BRAF突变患者（P=0.019）。然而，NRAS和BRAF突变不影响自诊断时起的总生存率（P=0.7）。综上所述，不同的基因型与几个关键临床和病理参数的差异相关，表明不同原癌基因突变的黑色素瘤肿瘤在生物学上存在差异。(c) 2006年Lippincott Williams & Wilkins。
We have previously demonstrated the use of pyrosequencing to investigate NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog] mutations in melanoma biopsies. Here, we expanded the analysis to include BRAF (V-raf murine sarcoma viral oncogene homolog 1311), another member of the Ras-Raf-mitogen-activated protein kinase (MAPK) signalling pathway, and analysed a total of 294 melanoma tumours from 219 patients. Mutations in BRAF exons 11 and 15 were identified in 156 (53%) tumours and NRAS exon 2 mutations in 86 (29%) tumours. Overall, mutations in NRAS or BRAF were found in 242 of 294 tumours; (82%) and were found to be mutually exclusive in all but two cases (0.7%). Multiple metastases were analysed in 57 of the cases and mutations were identical in all except three, indicating that BRAF and NRAS mutations occur before metastasis. Association with preexisting nevi was significantly higher in BRAF mutated tumours (P=0.014). In addition, tumours with BRAF mutations showed a significantly more frequent moderate to pronounced infiltration of lymphocytes (P=0.013). NRAS mutations were associated with a significantly higher Clark level of invasion (P=0.022) than BRAF mutations. Age at diagnosis was significantly higher in tumours with NRAS mutations than in those with BRAF mutations (P=0.019). NRAS and BRAF mutations, however, did not influence the overall survival from time of diagnosis (P=0.7). In conclusion, the separate genotypes were associated with differences in several key clinical and pathological parameters, indicating differences in the biology of melanoma tumours with different proto-oncogene mutations. (c) 2006 Lippincott Williams & Wilkins.