The Molecular Basis of Lynch-like Syndrome

  • Gardenia Vargas-Parra
  • Matilde Navarro
  • Marta Pineda
  • Gabriel Capellá


Lynch-like syndrome (LLS) refers to individuals with MMR-deficient Lynch syndrome (LS) spectrum tumors (in the absence of MLH1 methylation), in which no pathogenic germline mutation has been identified. Patients and their first-degree relatives are considered to have an intermediate risk of developing cancer between LS and the general population.

In this chapter, we aimed to review the most promising work in the area. Double somatic variants in MMR genes have been frequently reported (27–82% of LLS cases), while somatic promoter hypermethylation does not play a role. Carriers of germline MMR variants of unknown significance and missed mutations are part of LLS. Germline mutations in POLE and biallelic MUTYH mutations have been reported rarely. With the advent of NGS technologies, other genes like FAN1, BUB1, MCM9, and SETD2 are emerging as candidate responsible genes for LLS.


Lynch syndrome Lynch-like Next-generation sequencing Mismatch repair-deficiency Methylation Variant of unknown significance Double somatic hit 



Allele-specific expression


Colorectal cancer


Formalin-fixed paraffin embedded




Lynch-like syndrome


Loss of heterozygosity


Lynch syndrome


Mismatch repair


Microsatellite instability


Methylation-specific melting curve analysis


Next-generation sequencing


Peripheral blood leukocytes


Variant of unknown significance


Grant Support

This work was funded by the Spanish Ministry of Economy and Competitiveness (grant SAF2015–68016-R) and co-funded by FEDER (A Way to Build Europe) funds, the Spanish Association Against Cancer, the government of Catalonia (grant 2014SGR338), Fundación Mutua Madrileña (grant AP114252013), and RTICC MINECO Network RD12/0036/0031. This work is also supported by the Mexican National Council for Science and Technology (CONACyT) fellowship grant awarded to GV.


The authors declare no conflict of interest.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Gardenia Vargas-Parra
    • 1
  • Matilde Navarro
    • 1
  • Marta Pineda
    • 1
  • Gabriel Capellá
    • 1
  1. 1.Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL and CIBERONC, Hospitalet de LlobregatBarcelonaSpain

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