Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Next generation sequencing for tissue and plasma profiling of melanoma patients and plasma monitoring of treatment outcome: the MOBILY study

Date

09 Oct 2016

Session

Poster display

Presenters

Helena Linardou

Citation

Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379

Authors

H. Linardou1, S. Murray2, A. Laskarakis1, K. Giati1, C. Gouedard2, A. Tarampikou1, K. Tsigaridas1, D. Bafaloukos1

Author affiliations

  • 1 A' Oncology Clinic, Metropolitan Hospital, 185 47 - Athens/GR
  • 2 Molecular Oncology, BioPath Innovations, 15124 - Athens/GR
More

Resources

Abstract 3231

Background

Molecular profiling can identify potentially targetable mutations and facilitate treatment decisions. Recently BRAF mutant cell free DNA (cfDNA) was shown as an outcome predictor for melanoma patients on BRAF inhibitors (BRAFi). In this study we explore the potential of next generation sequencing (NGS) to molecularly characterise tissue and plasma and monitor outcome of melanoma patients.

Methods

Tumour DNA was isolated from paraffin blocks and cfDNA from plasma prospectively collected from melanoma patients. Deep sequencing using multigene panels (22 genes-tumour, 5 key genes-cfDNA) was performed by NGS on Ion Torrent. Plasma samples were collected at baseline, first month, best response and progression. Tissue:plasma concordance was assessed at baseline. Tumour burden and outcome were correlated with mutational load (cfDNA) assessed by % allelic frequency.

Results

Tissue and plasma samples were analysed for concordance from 43 metastatic melanoma (MM) patients (20 men 23 women, med age 62 yrs, 36 cutaneous 4 mucosal 2 ocular). Mutations were detected in 9 genes (BRAF 27, NRAS 3, KIT 2, GNAQ 1, KRAS 1, MAP2K1 1, MC1R 3, CDKN2A 2, p53 1, AKT3 1). Five patients had >1 mutation detected. A young patient with highly resistant MM had 4 simultaneous mutations (2 in resistance genes MAP2K1 and KRAS). Mutational concordance tissue:plasma was 72% (BRAF, NRAS). Seven patients with BRAF mutant MM in long remission with BRAFi had undetectable cfDNA mutational loads. Serial plasma samples were analysed from 3 BRAF mutant patients currently on BRAFi and 1 BRAF mutant patient on immune checkpoint inhibitor (IO). BRAF allelic load dramatically reduced to undetectable levels at 1st month of BRAFi, almost one month before radiological response. Interestingly, significant reduction of mutation levels was detected in the patient on IO correlating with rapid clinical response. Further patient analysis will be presented.

Conclusions

NGS tissue profiling is clinically relevant for melanoma providing prognostic information and cfDNA monitoring by NGS is feasible. In our population, serial plasma mutation assessment was in agreement with the clinical course and should be further explored as a monitoring tool of outcome.

Clinical trial identification

Legal entity responsible for the study

Metropolitan Hospital Scientific & Ethics Institutional Board

Funding

Hellenic Society for the Study of Melanoma (ELEMMEL)

Disclosure

All authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings