Detecting copy number alterations of oncogenes in cell-free DNA to monitor treatment response in acral and mucosal melanoma

• Published in: Journal of dermatological science 2020-03, Vol.97 (3), p.172-178
• Main Authors: Mikoshiba, Asuka, Ashida, Atsuko, Sakaizawa, Kaori, Kiniwa, Yukiko, Okuyama, Ryuhei
• Format: Article
• Language: English
• Subjects: Acral melanoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Cell-Free Nucleic Acids - blood; Cell-Free Nucleic Acids - genetics; Circulating tumor DNA; Copy number alteration; Cyclin D1 - genetics; Cyclin-Dependent Kinase 4 - genetics; Disease Progression; DNA Copy Number Variations; Droplet digital PCR; Female; Humans; Male; Melanoma - blood; Melanoma - diagnosis; Melanoma - genetics; Melanoma - therapy; Middle Aged; Mucosal melanoma; Mucous Membrane - diagnostic imaging; Mucous Membrane - pathology; Proto-Oncogene Proteins c-kit - genetics; Response Evaluation Criteria in Solid Tumors; Skin - diagnostic imaging; Skin - pathology; Skin Neoplasms - blood; Skin Neoplasms - diagnosis; Skin Neoplasms - genetics; Skin Neoplasms - therapy; Tomography, X-Ray Computed
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2020.01.001

•Copy number of KIT, CDK4, and CCND1 often increases in acral/ mucosal melanomas.•Copy number alteration in these genes can be detected in blood using digital PCR.•The plasma copy number ratio is affected by tumor copy number and tumor volume.•The change in plasma copy number is correlated with clinical outcome.•The plasma copy number ratio may be useful as a biomarker of melanoma progression. Reliable biomarkers are necessary for assessment of treatment responses. Acral and mucosal melanomas are commonly associated with copy number (CN) alterations rather than specific point mutations, with CN alterations inKIT, CDK4, and CCND1 occurring frequently. Cell-free DNA is released to peripheral blood by both normal and tumor cells, and therefore contains the same genetic alterations present in the source tumor. To investigate the usefulness of detecting CN alterations in oncogenes in cell-free DNA for monitoring treatment response in acral and mucosal melanomas. We isolated cell-free DNA from peripheral blood and assessed the CN alterations in the cell-free DNA. Using droplet digital PCR, we examined CN alterations ofKIT, CDK4, and CCND1 in tumors from 37 melanoma patients (acral, n = 27; mucosal, n = 10) and peripheral blood from 24 melanoma patients (acral, n = 17; mucosal, n = 7). CN gain was detected in at least one of the genes examined in 62.9 % (17/27) of acral melanomas and 70 % (7/10) of mucosal melanomas. CN gains were also detected in the plasma of some patients. Furthermore, plasma CN ratio was correlated with clinical condition. This correlation was especially clear in patients with high CN ratios in tumors and high tumor burdens. Plasma CN ratios may be useful for evaluating treatment responses in patients with acral and mucosal melanoma.