Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933255 | PMC |
http://dx.doi.org/10.1038/s41467-021-21576-8 | DOI Listing |
Expert Rev Respir Med
December 2024
Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Introduction: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane regulator (CFTR) gene, leading to progressive lung disease and systemic complications. Lung disease remains the primary cause of morbidity and mortality, making early detection of lung function decline crucial. The Lung Clearance Index (LCI), derived from the multiple breath washout (MBW) test, has emerged as a sensitive measure for identifying early airway disease.
View Article and Find Full Text PDFBMC Palliat Care
December 2024
Division of Radiation Oncology, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, T2N 4N2, Alberta, Canada.
Am J Med Genet A
December 2024
Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar.
The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12.
View Article and Find Full Text PDFMol Biol Cell
December 2024
Department of Biomedical Sciences, School of Veterinary Medicine.
Actin is an essential component of the cytoskeleton in every eukaryotic cell. Cytoplasmic β-and γ-actin are over 99% identical to each other at the protein level, but are encoded by different genes and play distinct roles in vivo. Blood cells, especially red blood cells (RBC), contain almost exclusively β-actin, and it has been generally assumed that this bias is dictated by unique suitability of β-actin for RBC cytoskeleton function due to its specific amino acid sequence.
View Article and Find Full Text PDFProtein Sci
January 2025
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
There is strong interest in accurate methods for predicting changes in protein stability resulting from amino acid mutations to the protein sequence. Recombinant proteins must often be stabilized to be used as therapeutics or reagents, and destabilizing mutations are implicated in a variety of diseases. Due to increased data availability and improved modeling techniques, recent studies have shown advancements in predicting changes in protein stability when a single-point mutation is made.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!