Familial Cancer

, Volume 17, Issue 3, pp 421–427 | Cite as

An exploration of genotype-phenotype link between Peutz-Jeghers syndrome and STK11: a review

  • Julian Daniell
  • John-Paul Plazzer
  • Anuradha Perera
  • Finlay Macrae


Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome. Clinical features include hamartomatous polyps, mucocutaneous pigmentation and an increased predisposition towards developing malignancy. Variants in STK11, a tumour suppressor gene, located on Chromosome 19, predispose to PJS. Peutz-Jeghers Syndrome is associated with increased rates of malignancy, particularly gastrointestinal. However, PJS is also associated with increased gynaecological, testicular and thyroid papillary malignancy. Truncating variants in STK11 are thought to predispose to a more severe phenotype. Phenotype severity is based on earlier onset of gastrointestinal pathology arising from the polyps, such as intussusception or earlier onset malignancy. Missense variants are generally considered less severe than truncating variants. There remain a large number of variants of undetermined significance. Studies have attempted to correlate the location of variants with impact on protein structure and overall severity of the PJS phenotype. The results from these cohort studies have consistently found a non-random distribution of variants. Nevertheless, a consensus on phenotype severity based on variant location is yet to be established. A centralised database that collates all known variants would facilitate the interpretation of these variants, best under the governance of an international disease-specific organisation (InSiGHT). In particular, it could help explore the significance of variants based on their type or location. Understanding the genotype-phenotype link between STK11 variants and PJS could allow more personalised care for PJS patients and their families via appropriate risk stratification and personalised and targeted cancer screening.


Peutz-Jeghers syndrome STK11 InSiGHT Hereditary tumour syndrome 



Adenoma malignum of the cervix


Adenosine monophosphate-activated protein kinase


Bronchioloalveolar carcinoma


C-terminal flanking tail


Glutathione peroxidase 4


Human Gene Variant Database


International Society for Gastrointestinal Tumors


Liver kinase B1


Microtubule affinity regulating kinases


Multiplex ligation-dependent probe amplification


Mouse protein 25


Peutz-Jeghers syndrome


Strawberry notch homolog 2


Sex cord tumour with annular tubules


Serine-threonine kinase 11


Ste20-related adaptor



The funding was provided by Cancer Council of Victoria and Royal Melbourne Hospital Foundation.


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  1. 1.The University of MelbourneMelbourneAustralia
  2. 2.The Royal Melbourne HospitalMelbourneAustralia

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