A novel ribosomal protein 20 variant in a family with unexplained colorectal cancer and polyposis

Thompson, B. A.; Snow, A. K.; Koptiuch, C.; Kohlmann, W. K.; Mooney, R.; Johnson, S.; Huff, C.; Yu, Y.; Teerlink, C. C.; Feng, B.-J.; Neklason, D. W.; Cannon-Albright, L. A.; Tavtigian, S. V.

doi:10.1101/2019.12.16.877084

bioRxiv · 10.1101/2019.12.16.877084

A novel ribosomal protein 20 variant in a family with unexplained colorectal cancer and polyposis

Thompson, B. A.·Snow, A. K.·Koptiuch, C.·Kohlmann, W. K.·Mooney, R.·Johnson, S.·Huff, C.·Yu, Y.·Teerlink, C. C.·Feng, B.-J.·Neklason, D. W.·Cannon-Albright, L. A.·Tavtigian, S. V.

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Abstract

Colorectal cancer (CRC) has a large hereditary component, which is only partially explained by known genetic causes. Recently, variants in ribosomal protein S20 (RPS20, [OMIM: 603682]) were identified in a family with familial CRC type X and in a CRC cancer case-control screen. This study describes a novel splice donor variant in RPS20, NM_001023.3:c.177+1G>A. It segregates with CRC [OMIM: 114500] and polyposis [HP: 0200063] within the probands family. Reverse transcription-polymerase chain reaction (RT-PCR) confirms the variant results in two aberrantly-spliced transcripts that are absent in controls. The location of the novel RPS20 variant is near two previously-reported truncating RPS20 variants associated with CRC. DNA from colon adenocarcinoma showed no evidence of loss-of-heterozygosity, supporting a haploinsufficiency or dominant negative disease mechanism. These findings support designation of RPS20 as a CRC predisposition gene, and expand the phenotypic spectrum of RPS20 truncating variants to include polyposis.

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Thompson, B. A., Snow, A. K., Koptiuch, C., Kohlmann, W. K., Mooney, R., Johnson, S., Huff, C., Yu, Y., Teerlink, C. C., Feng, B.-J., Neklason, D. W., Cannon-Albright, L. A., Tavtigian, S. V.. 2019-12-16. A novel ribosomal protein 20 variant in a family with unexplained colorectal cancer and polyposis. https://doi.org/10.1101/2019.12.16.877084

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