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Evidence suggests that germline RNF43 mutations are a rare cause of serrated polyposis
  1. Isabel Quintana1,2,3,
  2. Raquel Mejías-Luque4,5,
  3. Mariona Terradas1,2,
  4. Matilde Navarro1,2,3,
  5. Virginia Piñol6,7,
  6. Pilar Mur1,2,3,
  7. Sami Belhadj1,2,3,
  8. Elia Grau1,2,
  9. Esther Darder8,
  10. Ares Solanes9,
  11. Joan Brunet1,3,8,
  12. Gabriel Capellá1,2,3,
  13. Markus Gerhard4,5,
  14. Laura Valle1,2,3
  1. 1 Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain
  2. 2 Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, Barcelona, Spain
  3. 3 Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
  4. 4 Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Munich, Germany
  5. 5 German Centre for Infection Research (DZIF), Partner Site Munich, Munich, Germany
  6. 6 Digestive Unit, Hospital Universitario de Girona Dr Josep Trueta, Girona, Spain
  7. 7 School of Medicine, University of Girona, Girona, Spain
  8. 8 Hereditary Cancer Program, Catalan Institute of Oncology, IDIBGi, Girona, Spain
  9. 9 Hereditary Cancer Program, Catalan Institute of Oncology, Badalona, Spain
  1. Correspondence to Dr Laura Valle, Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de Llobregat, Barcelona 08908, Spain; lvalle{at}

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We read with interest the work by Yan et al published in Gut.1 The serrated (hyperplastic) polyposis syndrome (SPS) is a heterogeneous disease defined by the presence of multiple serrated polyps throughout the colon,2 causing an increased risk (16%) of colorectal cancer (CRC).3 By performing whole-exome sequencing in 20 SPS families, Gala et al identified a germline mutation, c.338C>A (p.R113*), in the RING-type E3 ubiquitin ligase RNF43, an inhibitor of the Wnt pathway, in two independent families.4 The c.394C>T (p.R132*) mutation was subsequently identified in two SPS-affected members of one family, supporting a causal role in SPS.5 In the study by Yan et al whole-exome sequence analysis of four SPS families identified a deleterious germline mutation, c.953–1G>A (p.E318fs), in six members of one family, five fulfilling the WHO criteria for SPS.1 Buchanan et al assessed the mutation status of RNF43 in 74 selected SPS families, identifying two rare missense variants, c.443C>G (p.A148G) and c.640C>G (p.L214V), predicted deleterious by in silico algorithms, in two families. No carriers of p.R113* or p.R132* were detected in 221 additional patients with SPS.6

Mutation screening of RNF43 was carried out by Sanger sequencing in …

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  • IQ, RM-L and MT contributed equally.

  • Contributors LV conceived the study. LV, RM-L, MG and GC contributed to the study design. IQ, RM-L, MT, SB and PM performed the experiments. MN, VP, EG, ED, AS, JB and GC were responsible for the selection and recruitment of patients and for the accrual samples. LV wrote the manuscript with the assistance and final approval of all authors.

  • Funding This work was supported by the Spanish Ministry of Economy and Competitiveness, cofunded by FEDER funds – a way to build Europe – (grants SAF2016-80888-R and SAF2015-68016-R, and Juan de la Cierva postdoctoral fellowship (PM)); Instituto de Salud Carlos III (CIBERONC CB16/12/00234) and the Government of Catalonia (Pla estratègic de recerca i innovació en salut (PERIS) and 2014SGR338).

  • Competing interests None declared.

  • Ethics approval Ethics Committee of Institut d’Investigació Biomèdica de Bellvitge (IDIBELL).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Experimental conditions, primer sequences and descriptive data of the studied patients are available upon request (