The iMYC trial is a biomarker-driven study in advanced OG cancer that prospectively screens patients for MYC amplification to assess the feasibility of ibrutinib therapy. MYC is implicated in OG cancer carcinogesis and as the acquisition of fitness enhancing mutations can drive tumour progression and treatment resistance, we present data from the screening component of the study evaluating the frequency and diversity of MYC amplification using FISH and ddPCR analysis of primary OG tumours and circulating tumour (ct)DNA.
To find potential on-chromosome (chr) 8 references for the MYC gene for the purposes of ddPCR, OG tumour sample copy number data were obtained from cBioportal using the CGDS-R package. A dual probe FISH assay to detect MYC amplification was optimised on archival OG tumour samples where centrometric probes for chr 8 and probes mapping specifically to the coding region of the MYC gene (exons 1-3) were used to distinguish between increased copies of chr 8 and extra copies of MYC.
To date 96 archival tumour samples have successfully undergone FISH analysis with MYC amplification seen in 26/96 (27%). The % of cells with MYC amplification ranged widely between samples (median 57.5, range 11-94%). Intra-tumour heterogeneity was seen: 19/26 (73%) amplified samples showed a range of differing amplification ratios within the tumour specimen (bartlett test for equal variance p
This study represents the first attempt to screen for MYC amplification prospectively in advanced OG cancer and illustrates the utility of FISH in assessing clonal diversity and visualisation of extrachromosomal amplifications. Using a novel ddPCR assay we have detected MYC amplifications from both archival tumour and ctDNA in homogeneous and highly amplified cases however the ddPCR assay is not optimal in detecting small clonal subpopulations of amplified cells in OG cancer.
Clinical trial identification
Legal entity responsible for the study
Royal Marsden NHS Foundation Trust oundation Trust
D. Cunningham: Research funding from Roche, Amgen, Celgene, Merck, BMS, Novartis, Astra Zeneca, Bayer, Merrimack, Medimmune, Clovis, I. Chau: Advisory Board: Sanofi Oncology, Eli-Lilly, Bristol Meyers Squibb, MSD, Bayer, Roche, Five Prime Therapeutics; Research funding: Janssen-Cilag, Sanofi Oncology, Merck-Serono, Novartis Honorarium: Taiho, Pfizer, Amgen, Eli-Lilly, Gilead Science. All other authors have declared no conflicts of interest.