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  • Review Article
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MUTYH-associated tumor syndrome: The other face of MAP

Oncogene volume 41, pages 2531–2539 (2022)Cite this article

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Abstract

MUTYH gene is involved in the base excision repair (BER) mechanism and its pathogenic alterations are associated with colorectal polyposis and cancer. MUTYH-associated polyposis (MAP) is a condition which is inherited in an autosomal recessive manner. MAP patients, beyond colorectal cancer (CRC), may develop other types of tumors, including duodenal, breast, ovarian, pancreatic, bladder and skin cancers. Carriers of biallelic MUTYH likely pathogenic/pathogenic variants exhibit a high lifetime risk of CRC, though cancer risk evidence becomes less clear when monoallelic carriers and extraintestinal tumors are considered. However, several studies recently reported an increased genetic susceptibility to cancer also for carriers of germline monoallelic MUTYH mutations. Moreover, experimental evidence highlighted the MUTYH involvement in many other biological functions. In future, MUTYH mutation carriers might benefit from new target therapies involving the use of PD-1 or KRAS inhibitors. Therefore, “MUTYH-associated tumor syndrome” might be the most appropriate term, due to the multiplicity of tumors observed in MAP patients and different biological contexts in which MUTYH acts as a “playmaker”. In this Review, we will investigate the impact of germline mono- and biallelic MUTYH mutations on cancer risk, providing a proposal for clinical surveillance of mutation carriers.

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Fig. 1: Chromosome localization and functional domains of MUTYH.
Fig. 2: Mechanism of DNA damage repair induced by MUTYH.

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Acknowledgements

The authors thank Dr. Chiara Drago for the English language revision.

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Author notes

  1. These authors contributed equally: Luigi Magrin, Daniele Fanale, Chiara Brando.

  2. These authors jointly supervised this work: Antonio Russo, Viviana Bazan.

Authors and Affiliations

  1. Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127, Palermo, Italy

    Luigi Magrin, Daniele Fanale, Chiara Brando, Lidia Rita Corsini, Ugo Randazzo, Marianna Di Piazza, Vittorio Gurrera, Erika Pedone & Antonio Russo

  2. Medicine and Surgery School, University of Palermo, 90127, Palermo, Italy

    Tancredi Didier Bazan Russo

  3. Division of General and Oncological Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo, 90127, Palermo, Italy

    Salvatore Vieni & Gianni Pantuso

  4. Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127, Palermo, Italy

    Viviana Bazan

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  1. Luigi Magrin
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Contributions

LM, DF, CB, AR and VB conceived, wrote, and critically revised the manuscript with the contribution of LRC, UR, MDP, VG, EP, TDBR, SV, and GP; Literature data were acquired and analyzed by LM, DF, CB, LRC, UR, MDP, VG, EP, and TDBR; The figures of the manuscript were conceived and designed by CB, UR, MDP, VG, and TDBR; The tables were conceived and designed by LM, UR, MDP, VG, and TDBR; LRC, SV, GP, AR, and VB participated to the critical revision of the manuscript. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Antonio Russo.

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Magrin, L., Fanale, D., Brando, C. et al. MUTYH-associated tumor syndrome: The other face of MAP. Oncogene 41, 2531–2539 (2022). https://doi.org/10.1038/s41388-022-02304-y

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  • DOI: https://doi.org/10.1038/s41388-022-02304-y

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