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Recent discoveries in the molecular genetics of Lynch syndrome

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Abstract

Lynch syndrome is the inherited predisposition to cancer caused by a germline mutation in a DNA mismatch repair gene. The consequent tumors have a characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these tumors have a substantially greater number of mutations than non-MSI CRCs, and that the target mutations driving tumor behavior are also different from what occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that can create clinical confusion with that disease, including the acquired methylation of MLH1, Lynch-like syndrome, and Familial CRC-Type X. Patients with Lynch syndrome-associated CRCs have a substantially better prognosis, and there is growing evidence that this is due to the generation of immunogenic frameshift peptides as a consequence of defective DNA mismatch repair, and an effective immune response to the tumor.

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Authors and Affiliations

  1. GI Cancer Research Laboratory, Baylor University Medical Center, Dallas, TX, 75246, USA

    C. Richard Boland

  2. GI Cancer Research Laboratory, Baylor Scott & White Research Institute, H-250, 3500 Gaston Avenue, Dallas, TX, 75246, USA

    C. Richard Boland

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Correspondence to C. Richard Boland.

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Boland, C.R. Recent discoveries in the molecular genetics of Lynch syndrome. Familial Cancer 15, 395–403 (2016). https://doi.org/10.1007/s10689-016-9885-5

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