RNF43 pathogenic Germline variant in a family with colorectal cancer

Reger R. Mikaeel, Joanne P. Young, Yun Li, Nicola K. Poplawski, Eric Smith, Mehgan Horsnell, Wendy Uylaki, Yoko Tomita, Amanda R. Townsend, Jinghua Feng, Arne Zibat, Silke Kaulfuß, Christian Müller, Gökhan Yigit, Bernd Wollnik, Hamish Scott, Lesley Rawlings, Denae Henry, Cassandra Vakulin, Andrew DubowskyTimothy J. Price

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The role of RNF43 as a cause of an inherited predisposition to colorectal cancer (CRC) is yet to be fully explored. This report presents our findings of two individuals with CRC from a single family carrying a likely-pathogenic inherited germline variant in RNF43. The proband (III:1) and the proband's mother (II:2) were diagnosed with mismatch repair proficient CRCs at the age of 50 years and 65 years, respectively. Both patients had BRAFV600E mutated colon tumours, indicating that the CRCs arose in sessile serrated lesions. The germline variant RNF43:c.375+1G>A was identified in both patients. RNA studies showed that this variant resulted in an aberrantly spliced transcript, which was predicted to encode RNF43:p.Ala126Ilefs*50 resulting in premature termination of protein synthesis and was classified as a likely-pathogenic variant. Our report adds further evidence to the hereditary role of RNF43 as a tumour suppressor gene in colorectal tumorigenesis and supports the inclusion of RNF43 as a gene of interest in the investigation of CRC predispositions outside the setting of serrated polyposis.

Original languageEnglish
Pages (from-to)122-126
Number of pages5
JournalClinical Genetics
Volume101
Issue number1
Early online date19 Sept 2021
DOIs
Publication statusPublished - Jan 2022
Externally publishedYes

Keywords

  • Colorectal cancer
  • Germline variant
  • RNA splicing
  • RNF43
  • Serrated polyposis

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