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A comparative analysis of RAS variants in patients with disorders of somatic mosaicism.
Claire Hou, Ying-Chen; Evenson, Michael J; Corliss, Meagan M; Mahapatra, Lily; Aldawood, Ali; Carpentieri, David F; Chamlin, Sarah L; Kulungowski, Ann M; Madan-Khetarpal, Suneeta; Sebastian, Jessica; Pet, Mitchell A; Coughlin, Carrie C; Willing, Marcia C; Pearson, Gregory D; Setty, Bhuvana A; El-Haffaf, Zaki; Cottrell, Catherine E; Parikh, Bijal A; Krysiak, Kilannin; Schroeder, Molly C; Heusel, Jonathan W; Neidich, Julie A; Cao, Yang.
Afiliación
  • Claire Hou YC; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Evenson MJ; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Corliss MM; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Mahapatra L; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Aldawood A; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Carpentieri DF; Clinical Laboratory, Phoenix Children's Hospital, Phoenix, AZ.
  • Chamlin SL; Departments of Pediatrics and Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL; Division of Dermatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
  • Kulungowski AM; Division of Pediatric Surgery, Department of Surgery, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO.
  • Madan-Khetarpal S; Division of Medical Genetics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA.
  • Sebastian J; Division of Medical Genetics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA.
  • Pet MA; Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, Washington University, St. Louis, MO.
  • Coughlin CC; Division of Dermatology, Departments of Medicine and Pediatrics, Washington University School of Medicine, St. Louis, MO.
  • Willing MC; Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Pearson GD; Department of Pediatric Plastic and Reconstructive Surgery, Nationwide Children's Hospital, Columbus, OH.
  • Setty BA; Division of Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children's Hospital, Columbus, OH; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH.
  • El-Haffaf Z; Genetic Medicine Service, Montreal University Hospital (CHUM-CRCHUM), Montréal, Quebec, Canada.
  • Cottrell CE; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH.
  • Parikh BA; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Krysiak K; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Schroeder MC; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Heusel JW; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO; Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Neidich JA; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO; Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO.
  • Cao Y; Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO. Electronic address: cao.yang@wustl.edu.
Genet Med ; 25(3): 100348, 2023 03.
Article en En | MEDLINE | ID: mdl-36571464
PURPOSE: RAS genes (HRAS, KRAS, and NRAS) are commonly found to be mutated in cancers, and activating RAS variants are also found in disorders of somatic mosaicism (DoSM). A survey of the mutational spectrum of RAS variants in DoSM has not been performed. METHODS: A total of 938 individuals with suspected DoSM underwent high-sensitivity clinical next-generation sequencing-based testing. We investigated the mutational spectrum and genotype-phenotype associations of mosaic RAS variants. RESULTS: In this article, we present a series of individuals with DoSM with RAS variants. Classic hotspots, including Gly12, Gly13, and Gln61 constituted the majority of RAS variants observed in DoSM. Furthermore, we present 12 individuals with HRAS and KRAS in-frame duplication/insertion (dup/ins) variants in the switch II domain. Among the 18.3% individuals with RAS in-frame dup/ins variants, clinical findings were mainly associated with vascular malformations. Hotspots were associated with a broad phenotypic spectrum, including vascular tumors, vascular malformations, nevoid proliferations, segmental overgrowth, digital anomalies, and combinations of these. The median age at testing was higher and the variant allelic fraction was lower in individuals with in-frame dup/ins variants than those in individuals with mosaic RAS hotspots. CONCLUSION: Our work provides insight into the allelic and clinical heterogeneity of mosaic RAS variants in nonmalignant conditions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Malformaciones Vasculares / Mosaicismo Límite: Humans Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Malformaciones Vasculares / Mosaicismo Límite: Humans Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos