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. 2022 Jan;101(1):122-126.
doi: 10.1111/cge.14064. Epub 2021 Sep 27.

RNF43 pathogenic Germline variant in a family with colorectal cancer

Reger R Mikaeel  1   2   3   4 , Joanne P Young  1   2   3 , Yun Li  5 , Nicola K Poplawski  6   7 , Eric Smith  1 , Mehgan Horsnell  1 , Wendy Uylaki  1 , Yoko Tomita  1 , Amanda R Townsend  1 , Jinghua Feng  8   9 , Arne Zibat  5 , Silke Kaulfuß  5 , Christian Müller  5 , Gökhan Yigit  5 , Bernd Wollnik  5   10 , Hamish Scott  3   8   9   11 , Lesley Rawlings  11 , Denae Henry  11 , Cassandra Vakulin  11 , Andrew Dubowsky  12 , Timothy J Price  1   3
Affiliations

RNF43 pathogenic Germline variant in a family with colorectal cancer

Reger R Mikaeel et al. Clin Genet. 2022 Jan.

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.

Keywords: Colorectal cancer; Germline variant; RNA splicing; RNF43; Serrated polyposis.

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References

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