{
  "id": 10719112,
  "title": "Genomic correlates of metastatic competence and progression in human melanoma",
  "url": "https://urgent.news/2026/09/29/genomic-correlates-of-metastatic-competence-and-progression-in-human",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-29T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753695v1?rss=1"
  },
  "original_language": "en",
  "account": "A comprehensive analysis of 247 stage I/II primary cutaneous melanomas and 60 matched metastases has shed light on the genomic events that enable melanoma to disseminate. Researchers found that key genomic alterations, rather than oncogenic point mutations, were linked to metastatic competence. These alterations included somatic copy-number changes and global chromosomal instability, which drove metastatic progression. The study introduced a novel six-gene copy-number signature, called OncoCycle, which could predict relapse in melanoma patients, independent of established clinicopathological features. This OncoCycle signature predicted relapse by identifying amplifications of CDK4, MCL1, and CD276, as well as biallelic loss of CDKN2A, CDKN2B, and TP53BP1. Moreover, the research revealed that metastatic progression was driven by ongoing copy-number evolution and decreased intra-tumoural heterogeneity, rather than the acquisition of new point mutations. The findings also demonstrated that metastatic seeding clones preserved OncoCycle alterations from the primary tumour, and clonal reconstruction showed both monoclonal and polyclonal dissemination. Spatial transcriptomics allowed researchers to map the spatial distribution of copy-number-defined metastatic subclones within the tumour and its surrounding environment. Overall, these results suggest that metastatic competence is primed early by focal copy-number alterations on a backdrop of chromosomal instability, which is then further refined by continued copy-number evolution during dissemination and spatial interactions with the tumour microenvironment.",
  "summary": "Genomic events and their timing that grant a primary tumour the competence to disseminate remain poorly defined. We performed sequencing of 247 stage I/II primary cutaneous melanomas (CMs) and 60 matched metastases without intervening therapy from a prospectively followed registry cohort with a median followup of 92 months, integrating copy-number, mutational, protein and spatial-transcriptomic…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}