title: Synonymous Somatic Variants in Human Cancer Are Not Infamous: A Plea for Full Disclosure in Databases and Publications.
abstract: Single-nucleotide variants (SNVs) are the most frequent genetic changes found in human cancer. Most driver alterations are missense and nonsense variants localized in the coding region of cancer genes. Unbiased cancer genome sequencing shows that synonymous SNVs (sSNVs) can be found clustered in the coding regions of several cancer oncogenes or tumor suppressor genes suggesting purifying selection. sSNVs are currently underestimated, as they are usually discarded during analysis. Furthermore, several public databases do not display sSNVs, which can lead to analytical bias and the false assumption that this mutational event is uncommon. Recent progress in our understanding of the deleterious consequences of these sSNVs for RNA stability and protein translation shows that they can act as strong drivers of cancer, as demonstrated for several cancer genes such as TP53 or BCL2L12. It is therefore essential that sSNVs be properly reported and analyzed in order to provide an accurate picture of the genetic landscape of the cancer genome.
authors.affiliation: Sorbonne Université, UPMC Univ Paris 06, Paris, F-75005, France.|INSERM, U1138, Centre de Recherche des Cordeliers, Paris, France.|Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska (CCK) R8:04, Stockholm, SE-171 76, Sweden.
authors.forename: Thierry
authors.initials: T
authors.lastname: Soussi
authors.affiliation: Generade Centre of Expertise Genomics and University of Applied Sciences Leiden, Leiden, 2333 CL, The Netherlands.
authors.forename: Peter E M
authors.initials: PE
authors.lastname: Taschner
authors.affiliation: Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Yardena
authors.initials: Y
authors.lastname: Samuels
mesh_terms: D016147:Genes, Tumor Suppressor; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014176:Protein Biosynthesis / Q000235:genetics; D020871:RNA Stability / Q000235:genetics
keywords: TP53; cancer; database; synonymous variants