Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.
Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.
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DOI：
10.1038/sj.bjc.6605371
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发表时间：
2009-11-17
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究探讨了循环游离DNA（cfDNA）作为BRAF突变检测来源的潜在临床效用，该来源用于入组AZD 6244（一种特异性MEK 1/2抑制剂）II期研究的晚期黑色素瘤患者。使用扩增难治性突变系统等位基因特异性PCR检测BRAF突变。在来自入组研究的126名患者和来自94个匹配的肿瘤样品的血清来源的cfDNA中评估BRAF突变状态。在94例肿瘤样本中，发现45例（47.9%）为BRAF突变阳性（BRAF+）。在126个样本中的33个（26.2%）样本中，血清来源的cfDNA为BRAF+，包括5个肿瘤数据不可用的样本。在BRAF+肿瘤中，25/45（55.6%）在cfDNA中为BRAF+。在肿瘤为阴性的三个病例中，cfDNA为BRAF+。与肿瘤BRAF+但cfDNA BRAF阴性患者相比，BRAF+肿瘤和cfDNA患者的无进展生存期（PFS）无显著差异，表明cfDNA BRAF检测与III/IV期晚期黑色素瘤PFS预后不良无关。这些数据证明了晚期黑素瘤患者cfDNA中BRAF突变检测的可行性。未来的研究应旨在将BRAF突变检测纳入cfDNA中，以进一步验证该生物标志物用于患者选择。
This study investigated the potential clinical utility of circulating free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into a phase II study of AZD6244, a specific MEK1/2 inhibitor, in patients with advanced melanoma. BRAF mutations were detected using Amplification Refractory Mutation System allele-specific PCR. BRAF mutation status was assessed in serum-derived cfDNA from 126 patients enrolled into the study and from 94 matched tumour samples. Of 94 tumour samples, 45 (47.9%) were found to be BRAF mutation positive (BRAF+). Serum-derived cfDNA was BRAF+ in 33 of 126 (26.2%) samples, including in five samples for which tumour data were unavailable. Of BRAF+ tumours, 25 of 45 (55.6%) were BRAF+ in cfDNA. In three cases in which the tumour was negative, cfDNA was BRAF+. Progression-free survival (PFS) of patients with BRAF+ tumour and cfDNA was not significantly different compared with tumour BRAF+ but cfDNA BRAF-negative patients, indicating that cfDNA BRAF detection is not associated with poorer prognosis on PFS in stage III/IV advanced melanoma. These data demonstrate the feasibility of BRAF mutation detection in cfDNA of patients with advanced melanoma. Future studies should aim to incorporate BRAF mutation testing in cfDNA to further validate this biomarker for patient selection.
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评估血清 DNA 中表皮生长因子受体突变状态作为吉非替尼 (IRESSA) 反应的预测因子。
影响因子：
8.8
作者：
Kimura, H.;Suminoe, M.;Kasahara, K.;Sone, T.;Araya, T.;Tamori, S.;Koizumi, F.;Nishio, K.;Miyamoto, K.;Fujimura, M.;Nakao, S.
通讯作者：
Nakao, S.
DOI：
10.1093/jnci/dji432
发表时间：
2005-12-21
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Sozzi, G;Roz, L;Pastorino, U
通讯作者：
Pastorino, U
影响因子：
6.4
作者：
Daniotti, Maria;Vallacchi, Viviana;Rodolfo, Monica
通讯作者：
Rodolfo, Monica
影响因子：
4.1
作者：
Yancovitz, Molly;Yoon, Joanne;Polsky, David
通讯作者：
Polsky, David
影响因子：
56.9
作者：
MANSOUR, SJ;MATTEN, WT;AHN, NG
通讯作者：
AHN, NG