Poster Presentation 36th Lorne Cancer Conference 2024

Decoding Cellular Behaviour and Treatment Challenges at Different Sites of Melanoma Metastasis. (#118)

Veronica Aedo-Lopez 1 2 , Reem Saleh 1 , Xin Du 1 , Dane Vassiliadis 1 , Mark Dawson 1 , Riccardo Dolcetti 1 , Roberta Mazzieri 1 , Davide Moi 1 , Karen E Sheppard 1 , Grant A McArthur 1
  1. Peter MacCallum Cancer Centre, Melbourne, VICTORIA, Australia
  2. Medicine and Dentistry Health Sciences , University of Melbourne, Melbourne, VIC, Australia

Background: Melanoma, a highly metastatic skin cancer, exhibits variations in prognosis and response to therapy based on the affected organ. Patients with liver and brain metastasis have shorter survival compared to those with lung metastasis (1, 2). Additionally, the response to immunotherapy and targeted therapy differs among various organs (3, 4). Melanoma cell plasticity allows phenotype switching with no gain of mutations (5, 6) and both cell plasticity and intra-tumoural melanoma heterogeneity contribute to metastatic dissemination and resistance (5-7). 

Aims: This study aims to analyse cell sub-clones and their transcriptional phenotypes at different metastatic sites and in response to targeted therapy and/or immunotherapy. This will enhance our understanding of melanoma transcriptome behaviours and biological characteristics in diverse metastatic sites.

Methods:  C57BL/6 mice were injected intravenously with 0.5x106 barcoded YUMMER1.7PV1 GFP+/Luciferase+ to induce experimental metastasis in a syngeneic mouse model. Bioluminescence imaging (BLI) was performed once a week to monitor tumour growth and progression over time. YUMMER1.7PV1 murine melanoma cells are clinically relevant to human melanoma as they harbour genetic mutations in BRAF, PTEN and p16 (8). In addition, these cells have a high somatic mutation burden similar to human melanoma and are responsive to both targeted therapy (BRAF/MEK inhibitors) and immunotherapy. For tracking clones and analysing phenotypes at different metastatic sites, we will use Single-Cell Profiling and LIneage TRacing, SPLINTR, a barcoding technology recently developed, coupled with single cell RNA sequencing (scRNA-seq) to transcriptionally track individual cells overtime (9).

Results: Lung and liver metastases were induced by intravenous tumour cell implantation and were detected by BLI. The presence of barcodes in metastatic lesions have been demonstrated by DNA gel electrophoresis. DNA barcode sequencing for analysing barcodes in different metastatic site is undergoing.

Conclusions: This project will potentially provide new understanding of melanoma cell sub-clones, behaviours and their transcriptional phenotypes at different metastatic sites and in response to therapy.

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