Open AccessEarly detection of metastatic uveal melanoma by the analysis of tumor‐specific mutations in cell‐free plasma DNA
Author(s) -
Le Guin Claudia H. D.,
Bornfeld Norbert,
Bechrakis Nikolaos E.,
Jabbarli Leyla,
Richly Heike,
Lohmann Dietmar R.,
Zeschnigk Michael
Publication year - 2021
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.4153
Subject(s) - gnaq , melanoma , medicine , cell free fetal dna , metastasis , cancer , radiation therapy , uvea , cancer research , oncology , mutation , pathology , biology , gene , pregnancy , biochemistry , fetus , genetics , prenatal diagnosis
Background Eye salvaging therapy of malignant melanomas of the uvea can preserve the eye in most cases, but still about half of patients die from metastatic disease. Previous analyses of cell‐free DNA from plasma had shown detectable levels of tumor‐specific GNAQ / GNA11 mutations in patients with the clinical diagnosis of progressive disease. However, data on the time span that elapses from the detection of ctDNA in plasma to the clinical detection of metastases (diagnostic lead time) are missing. Methods We examined 135 patients with uveal melanoma. Cell‐free DNA was isolated from a total of 807 blood samples which were taken over a period of up to 41 months and analyzed for the presence of GNAQ / GNA11 mutations by deep amplicon sequencing. Results Twenty‐one of the 135 patients developed metastases or recurrence. A ctDNA signal was identified in the plasma of 17 of the 21 patients. In 10 patients, this ctDNA signal preceded the clinical diagnosis of metastasis by 2–10 months. In 10 other patients, a ctDNA signal was only detected in samples obtained shortly before or after radiotherapy. The presence of a ctDNA signal in 16 of the remaining 125 patients was linked to clinical manifestation of metastases ( n = 14) or tumor recurrence ( n = 2) with a sensitivity and specificity of 80% and 96%, respectively. Conclusion Detection of ctDNA in plasma can provide a diagnostic lead time over the clinical diagnosis of metastases or tumor recurrence. Longer lead times are to be expected if intervals between sampling are shortened.