Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients.
Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients.
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DOI：
10.1038/s41598-020-75792-1
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发表时间：
2020-10-29
影响因子：
4.6
通讯作者：
Vazquez VL
中科院分区：
文献类型：
--
作者：
Marczynski GT;Laus AC;Dos Reis MB;Reis RM;Vazquez VL
BRAF、NRAS和TERT突变发生在超过2/3的黑色素瘤中。它在患者血液中的检测，作为循环肿瘤DNA（ctDNA），代表了识别和监测转移性疾病的可能性。我们建议标准化液体活检平台，以识别晚期黑色素瘤患者血浆样本中BRAF、NRAS和TERT的热点突变，并研究其是否与临床结局相关。首先，我们使用肿瘤细胞系进行数字聚合酶链反应，以验证和确定每个检测方法的检测限（LOD），并筛选健康个体的血浆样本，以确定空白限（LOB）。然后，我们选择了19例III期和IV期患者，确定肿瘤组织中的体细胞突变状态，并在患者血浆中追踪它们。我们建立了一种特异性和灵敏度的方法，LOD范围为0.13%至0.37%，LOB范围为0至5.201个拷贝/反应。17/19例（89%）患者发生体细胞突变，其中7例（41%）患者的配对血浆中可检测到ctDNA。ctDNA检测与较短的无进展生存期相关（p = 0.01）。总之，我们的数据支持使用ctDNA作为预后生物标志物，表明具有可检测水平的患者具有不利的结果。
BRAF, NRAS and TERT mutations occur in more than 2/3 of melanomas. Its detection in patient’s blood, as circulating tumor DNA (ctDNA), represents a possibility for identification and monitoring of metastatic disease. We proposed to standardize a liquid biopsy platform to identify hotspot mutations in BRAF, NRAS and TERT in plasma samples from advanced melanoma patients and investigate whether it was associated to clinical outcome. Firstly, we performed digital polymerase chain reaction using tumor cell lines for validation and determination of limit of detection (LOD) of each assay and screened plasma samples from healthy individuals to determine the limit of blank (LOB). Then, we selected 19 stage III and IV patients and determined the somatic mutations status in tumor tissue and track them in patients’ plasma. We established a specific and sensitive methodology with a LOD ranging from 0.13 to 0.37%, and LOB ranging from of 0 to 5.201 copies/reaction. Somatic mutations occurred in 17/19 (89%) patients, of whom seven (41%) had ctDNA detectable their paired plasma. ctDNA detection was associated with shorter progression free survival (p = 0.01). In conclusion, our data support the use of ctDNA as prognosis biomarker, suggesting that patients with detectable levels have an unfavorable outcome.
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影响因子：
5.2
作者：
Diefenbach, Russell J.;Lee, Jenny H.;Rizos, Helen
通讯作者：
Rizos, Helen
影响因子：
4.6
作者：
de Unamuno Bustos B;Murria Estal R;Pérez Simó G;de Juan Jimenez I;Escutia Muñoz B;Rodríguez Serna M;Alegre de Miquel V;Llavador Ros M;Ballester Sánchez R;Nagore Enguídanos E;Palanca Suela S;Botella Estrada R
通讯作者：
Botella Estrada R
影响因子：
17.1
作者：
Bidard, Francois-Clement;Weigelt, Britta;Reis-Filho, Jorge S.
通讯作者：
Reis-Filho, Jorge S.
DOI：
10.1126/science.1229259
发表时间：
2013-02-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Huang FW;Hodis E;Xu MJ;Kryukov GV;Chin L;Garraway LA
通讯作者：
Garraway LA
影响因子：
28.2
作者：
Haber DA;Velculescu VE
通讯作者：
Velculescu VE