Open AccessLocus‐specific concordance of genomic alterations between tissue and plasma circulating tumor DNA in metastatic melanoma
Author(s) -
Calapre Leslie,
Giardina Tindaro,
Robinson Cleo,
Reid Anna L.,
AlOgaili Zeyad,
Pereira Michelle R.,
McEvoy Ashleigh C.,
Warburton Lydia,
Hayward Nicholas K.,
Khattak Muhammad A.,
Meniawy Tarek M.,
Millward Michael,
Amanuel Benhur,
Ziman Melanie,
Gray Elin S.
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12391
Subject(s) - liquid biopsy , melanoma , biology , cold pcr , biopsy , concordance , cancer research , microbiology and biotechnology , somatic cell , dna , gene , point mutation , mutation , pathology , genetics , cancer , medicine
Circulating tumor DNA (ct DNA ) may serve as a surrogate to tissue biopsy for noninvasive identification of mutations across multiple genetic loci and for disease monitoring in melanoma. In this study, we compared the mutation profiles of tumor biopsies and plasma ct DNA from metastatic melanoma patients using custom sequencing panels targeting 30 melanoma‐associated genes. Somatic mutations were identified in 20 of 24 melanoma biopsies, and 16 of 20 (70%) matched‐patient plasmas had detectable ct DNA . In a subgroup of seven patients for whom matching tumor tissue and plasma were sequenced, 80% of the mutations found in tumor tissue were also detected in ct DNA . However, TERT promoter mutations were only detected by dd PCR , and promoter mutations were consistently found at lower concentrations than other driver mutations in longitudinal samples. In vitro experiments revealed that mutations in promoter regions of TERT and DPH 3 are underrepresented in ct DNA . While the results underscore the utility of using ct DNA as an alternative to tissue biopsy for genetic profiling and surveillance of the disease, our study highlights the underrepresentation of promoter mutations in ct DNA and its potential impact on quantitative liquid biopsy applications.