NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing
NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing
复制标题
黑色素瘤中的 NRAS 和 BRAF 突变与临床特征的关系：基于焦磷酸测序突变筛查的研究
作者：
Esther Edlundh;Suzanne Egyha´zi;K. Omholt;Eva Ma˚nsson;A. Platz;J. Hansson;J. Lundeberg
我们以前已经证明了使用焦磷酸测序技术来研究黑色素瘤活检组织中的NRAS[神经母细胞瘤RAS病毒(v-ras)癌基因同源]突变。在这里，我们扩大了分析范围，包括Ras-Raf-丝裂原活化蛋白激酶(MAPK)信号通路的另一个成员BRAF(V-RAF小鼠肉瘤病毒癌基因同源B1)，并分析了来自219名患者的总共294个黑色素瘤肿瘤。在156个(53%)肿瘤中发现了BRAF外显子11和15的突变，在86个(29%)肿瘤中发现了NRAS外显子2突变。总体而言，在294个肿瘤中有242个(82%)发现了NRAS或BRAF的突变，除了两个(0.7%)外，所有的肿瘤都被发现是相互排斥的。分析了57例多发性转移病例，除3例外，所有病例的突变均相同，表明BRAF和NRAS突变发生在转移之前。在BRAF突变的肿瘤中，与先前存在的痣的关联性显著更高(P=0.014)。此外，具有BRAF突变的肿瘤显示中度至重度淋巴细胞浸润的频率明显更高(P=0.013)。与BRAF突变相比，NRAS突变与克拉克级别的侵袭性显著相关(P=0.022)。NRAS基因突变的肿瘤患者的确诊年龄显著高于BRAF基因突变的肿瘤患者(P=0.019)。然而，NRAS和BRAF突变并不影响确诊后的总存活率(P=0.7)。总之，不同的基因类型与几个关键的临床和病理参数的差异有关，这表明具有不同原癌基因突变的黑色素瘤肿瘤的生物学差异。
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 B1), 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.
影响因子：
11.2
作者：
Alexis Gorden;I. Osman;W. Gai;D. He;Wei-qing Huang;A. Davidson;A. Houghton;K. Busam;D. Polsky
通讯作者：
Alexis Gorden;I. Osman;W. Gai;D. He;Wei-qing Huang;A. Davidson;A. Houghton;K. Busam;D. Polsky
影响因子：
8
作者：
A. P. Albino;D. M. Nanus;I. R. Mentle;Carlos Cordon-Cardo;N. McNutt;Jan Bressler;Michael Andreeff
通讯作者：
A. P. Albino;D. M. Nanus;I. R. Mentle;Carlos Cordon-Cardo;N. McNutt;Jan Bressler;Michael Andreeff
影响因子：
6.5
作者：
Goel, Vikas K.;Lazar, Alexander J. F.;Haluska, Frank G.
通讯作者：
Haluska, Frank G.