Prevalence of germline MUTYH mutations among Lynch-like syndrome patients

Adela Castillejo, Gardenia Vargas, María Isabel Castillejo, Matilde Navarro, Víctor Manuel Barberá, Sara González, Eva Hernández-Illán, Joan Brunet, Teresa Ramón Y Cajal, Judith Balmaña, Silvestre Oltra, Sílvia Iglesias, Àngela Velasco, Ares Solanes, Olga Campos, Ana Beatriz Sánchez Heras, Javier Gallego, Estela Carrasco, Dolors González Juan, Ángel SeguraIsabel Chirivella, María José Juan, Isabel Tena, Conxi Lázaro, Ignacio Blanco, Marta Pineda, Gabriel Capellá, José Luis Soto

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65 Scopus citations


Background and aims Individuals with tumours showing mismatch repair (MMR) deficiency not linked to germline mutations or somatic methylation of MMR genes have been recently referred as having 'Lynch-like syndrome' (LLS). The genetic basis of these LLS cases is unknown. MUTYH-associated polyposis patients show some phenotypic similarities to Lynch syndrome patients. The aim of this study was to investigate the prevalence of germline MUTYH mutations in a large series of LLS patients. Methods Two hundred and twenty-five probands fulfilling LLS criteria were included in this study. Screening of MUTYH recurrent mutations, whole coding sequencing and a large rearrangement analysis were undertaken. Age, sex, clinical, pathological and molecular characteristics of tumours including KRAS mutations were assessed. Results We found a prevalence of 3.1% of MAP syndrome in the whole series of LLS (7/225) and 3.9% when only cases fulfilling clinical criteria were considered (7/178). Patients with MUTYH biallelic mutations had more adenomas than monoallelic (P = 0.02) and wildtype patients (P < 0.0001). Six out of nine analysed tumours from six biallelic MUTYH carriers harboured KRAS-p.G12C mutation. This mutation was found to be associated with biallelic MUTYH germline mutation when compared with reported series of unselected colorectal cancer cohorts (P < 0.0001). Conclusions A proportion of unexplained LLS cases is caused by biallelic MUTYH mutations. The obtained results further justify the inclusion of MUTYH in the diagnostic strategy for Lynch syndrome-suspected patients.

Original languageEnglish
Pages (from-to)2241-2250
Number of pages10
JournalEuropean Journal of Cancer
Issue number13
StatePublished - Sep 2014
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded by the Spanish Ministry of Economy and Competitiveness (grant SAF2012-33636 ); the Scientific Foundation Asociación Española Contra el Cáncer ; the Government of Catalonia (grant 2009SGR290 ), Fundación Mutua Madrileña (grant AP114252013 ), RTICC MINECO Network RD12/0036/0031 and RD12/0036/0008 , and the Biomedical Research Foundation from the Hospital of Elche (FIBElx-CO11/03). AC and M-IC are funded by Health and Biomedical Research Foundation from the Valencian Region ( FISABIO ). The Mexican National Council for Science and Technology (CONACyT) fellowship to GV. EH-I is recipient of a fellowship from the Fondo Investigación Sanitaria ISCIII (FI12/00233).


  • KRAS mutations
  • Lynch syndrome
  • MAP syndrome


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