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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients

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Marczynski, Gabriella Taques [1] ; Laus, Ana Carolina [1] ; dos Reis, Mariana Bisarro [1] ; Reis, Rui Manuel [2, 3, 1] ; Vazquez, Vinicius de Lima [1, 4, 5]
Total Authors: 5
[1] Barretos Canc Hosp, Mol Oncol Res Ctr, 1331 Antenor Duarte Villela St, BR-14784400 Barretos, SP - Brazil
[2] ICVS 3Bs PT Govt Associate Lab, Braga, Guimaraes - Portugal
[3] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga - Portugal
[4] Barretos Canc Hosp, Surg Dept Melanoma Sarcoma & Mesenchymal Tumors, Barretos - Brazil
[5] Barretos Sch Hlth Sci Dr Paulo Prata FACISB, Barretos - Brazil
Total Affiliations: 5
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 10, n. 1 OCT 29 2020.
Web of Science Citations: 0

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. (AU)

FAPESP's process: 18/14468-8 - Platform: liquid biopsy for melanomas
Grantee:Vinicius de Lima Vazquez
Support type: Regular Research Grants