Dataset Information

Multi-modal Omics Analysis of a Paediatric Melanoma Highlights Mechanisms Underlying Treatment Resistance [Seq]

ABSTRACT: Background Cutaneous malignant melanoma is a common cancer in adults but extremely rare in young children, affecting fewer than one child per million each year in Europe. Because of its rarity, most treatments for children are adapted from adult therapies, despite possible biological differences. This study aimed to explore the molecular features of a rare and aggressive melanoma in a 16-month-old patient to understand disease progression and treatment resistance. Methods We studied the tumour and metastases of a patient with a melanoma carrying an NRAS mutation, who received chemotherapy and immune checkpoint inhibitor treatment. The patient died 10 months after diagnosis. We used DNA methylation analysis, single nucleus RNA sequencing, and deep spatial transcriptomic profiling to examine genetic changes, gene activity, and their spatial distribution in both the primary tumour and lymph node metastases. Results Here we show that the tumour displayed high genetic and transcriptomic diversity. We identified increases in MITF and BRAF gene copies as likely key drivers of the aggressive disease, which were not detected at diagnosis. We also found activation of biological pathways, including VEGFA and WNT signalling, and abnormal activity of several genes linked to immune therapy response, with marked variation between tumour regions. Conclusions This case demonstrates that paediatric melanoma can harbour complex and spatially variable molecular changes that contribute to rapid disease progression and treatment failure. Our findings support incorporating detailed spatial transcriptional profiling into clinical assessment to better guide therapy in rare paediatric cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286410 | GEO | 2025/10/20

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Circulating tumor cells (CTCs) are critical in the development of distant organ tumor metastasis, and are associated with advanced cancer stage and poor patient outcome. Here, we present the first genome-wide nucleotide-level characterization of CTCs. Our single-nucleotide polymorphism (SNP) analysis in patients with melanoma involved: 1) global comparative genomic analysis of CTCs and matched regional metastases, 2) identification of key genomic aberrations in CTCs, 3) verification of these target genes in aggressive distant tumor metastases, and 4) evidence of selective expression and functional consequence of CTC-associated genes in melanomas. We report 131 aberrant loci in CTCs that are potentially pro-metastatic, and show that such expression of a 5-marker gene panel (CSMD2, CNTNAP5, FLJ14051, ADAM6, TRPM2) in melanomas confers prognostic utility. Successful treatment of melanoma requires understanding of the metastatic process and identification of patients with tumors most likely to develop aggressive metastatic disease. Melanomas are heterogeneous, and CTCs have long been recognized as vehicles for cancer spread, representing particularly aggressive tumor clones that can evolve into successful clinical metastases. Elucidation of genomic aberrations in CTCs will aid in the development of prognostic biomarkers and therapeutic strategies to target CTCs to prevent or control distant cancer spread. This study provides the first detailed genomic confirmation of the close relation between CTCs and tumor metastases, and illustrates how CTCs can be utilized as a novel approach and rational source for identification of pro-metastatic genes in cancer research. Three individual patient cohorts were utilized in the study. CNV and LOH loci were evaluated initially in metastatic melanoma patients (n=13) in a discovery cohort. SNP loci that harbored CNV/LOH in CTCs were then separately verified for: (a) presence in distant organ metastasis (AJCC Stage IV melanoma) (n=27), and (b) relevance to prognosis in regional melanoma metastasis (AJCC Stage III melanoma) (n=35). The first discovery patient cohort group was utilized for capture of CTCs, and consisted of peripheral blood mononuclear cell (PBMC) and tumor specimens from metastatic melanoma patients (n=13). CTC-related loci were verified in a second cohort of patients with Stage IV distant organ metastases (n=27), including 15 brain, 4 lung, and 8 gastrointestinal (bowel, liver) metastases. The third patient cohort consisted of early passage (<12) established melanoma cell lines derived from 35 regional melanoma metastases (Stage III) for evaluation of the prognostic utility of the CTC-associated aberrant loci.

Dataset Information

Multi-modal Omics Analysis of a Paediatric Melanoma Highlights Mechanisms Underlying Treatment Resistance [Seq]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets