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Circulating tumor DNA (ctDNA) in metastatic uveal melanoma (MUM): Correlation with outcome in 87 patients (pts) from Institut Curie
Author(s) -
PIPERNONEUMANN S,
MADIC J,
MARIANI P,
RAMPANOU A,
SERVOIS V,
BIDARD FC,
MILDER M,
CASSOUX N,
DESJARDINS L,
STERN MH,
LANTZ O
Publication year - 2013
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2013.4442.x
Subject(s) - medicine , gnaq , metastasis , oncology , gastroenterology , cancer , pathology , mutation , biology , biochemistry , gene
Purpose CtDNA can be detected in the plasma of MUM pts using a real‐time PCR based on the pyrophosphorolysis‐activated polymerization (bi‐PAP) targeting the most frequent GNAQ and GNA11 mutations present in 85% of UM (Madic et al, 2012). Methods May 2011‐March 2013:87 MUM pts were included in 3 prospective studies to assess the bi‐PAP assay and analyse clinical and outcome correlations. Results Median (med) age 57, primary tumor med diameter 15 mm; enucleation 32, proton beam 52, iodine disk 3. Enucleated eyes showed mostly mixed histotype and genomic high risk by array‐CGH: 8q gain and/or 3p loss. With a med disease free interval of 39 months (mo), 83 pts developed liver metastases first, with radiological miliary disease in 55; 4 had extra hepatic lesions without liver involvement. 35 pts were enrolled at the time of metastasis diagnostic. With a med follow‐up of 8 mo, 28 patients had disease progression and 34 died of metastasis. The med survival was 13 mo. Tumor samples were available in 82 pts, genotyping is ongoing for 8. GNAQ 626A>T or A>C, GNA11 626A>T and rare mutations were found in 9, 19, 26 is and 6 cases respectively; 14 were wild‐type tumors. CtDNA was detected in 51/54 samples (med 30 copies/ml, range 1‐11421) and correlated with the metastatic tumor burden as assessed by liver MRI (med 64 cm3, range 0.2‐7384). Correlation with progression‐free and overall survival will be presented. Conclusion ctDNA is a promising tool to assess the tumor burden and the micrometastatic dissemination of uveal melanoma, and a potential biomarker to evaluate the efficacy of targeted therapies in pts carrying GNA Q/11 mutated tumors.