The SALSA MLPA probemix P101 STK11 is an in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative assay for the detection of deletions or duplications in the human STK11 gene in genomic DNA isolated from human peripheral whole blood specimens. P101 STK11 is intended to confirm a potential cause of and clinical diagnosis for Peutz-Jeghers syndrome and for molecular genetic testing of at-risk family members.

For the full intended purpose, see the product description.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by benign gastrointestinal polyps, hyper-pigmented skin spots, and an increased risk (>15x) of malignant epithelial cancers at various anatomic sites (colorectal, gastric, pancreatic, breast, uterine cervix, and ovarian cancers). The prevalence of this condition is uncertain; estimates range from 1 in 25.000 to 300.000 individuals. The age of onset of symptoms from polyps is variable, with some children developing symptoms within the first few years of life. About one-third of patients with PJS are diagnosed before the age of 10 years and up to 60% of the cases develop their first clinical manifestations before the age of 30 years. The basis of familial PJS is a germline mutation in the STK11 tumour suppressor gene, located in chromosomal region 19p13.3.

STK11 alterations in PJS patients comprise mainly point mutations and it is estimated that ~15-20% of pathogenic mutations in the STK11 gene are attributed to large deletions/duplications, which is comparable between PJS populations (Borun et al. 2015, Chow et al. 2006, Orellana et al. 2013). The STK11 gene is frequently inactivated by deletions or by point mutations in several cancer types, including lung and cervical cancer, and inactivation is suggested to be associated with disease progression (Ji et al. 2007, Wingo et al. 2009).

More information is available at https://www.ncbi.nlm.nih.gov/books/NBK1266/.

SALSA MLPA Probemix P101 STK11 is CE-marked under the IVDD for in vitro diagnostic (IVD) use in Europe. This assay has also been registered for IVD use in Israel.

This assay is for research use only (RUO) in all other territories.

Inclusion of a positive sample is usually not required, but can be useful for the analysis of your experiments. MRC Holland has very limited access to positive samples and cannot supply such samples. We recommend using positive samples from your own collection. Alternatively, you can use positive samples from an online biorepository, such as the Coriell Institute.

We have no information about specific commercially available positive samples that can be used with this product.

Various related products

• P158 JPS: Contains probes for the BMPR1A, SMAD4 and PTEN genes.
• P225 PTEN: Contains probes for the PTEN gene.

General MLPA resources

• MLPA technique overview
• Coffalyser.Net overview

MLPA education

• Getting started with MLPA
• Using Coffalyser.Net to analyse MLPA data
• Help centre with other learning resources

Selected publications using P101 STK11

• Aretz S et al. (2005). High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome. Hum Mutat. 26:513-9.
• De Leng WWJ et al. (2007). Genetic defects underlying Peutz-Jeghers syndrome (PJS) and exclusion of the polarity-associated MARK/Par1 gene family as potential PJS candidates. Clin Genet. 72:568-73.
• De Wilde RF et al. (2011). Analysis of LKB1 mutations and other molecular alterations in pancreatic acinar cell carcinoma. Mod Pathol. 24:1229-36.
• Fang R et al. (2014). Integrative genomic analysis reveals a high frequency of LKB1 genetic alteration in Chinese lung adenocarcinomas. J Thorac Oncol. 9:254-8.
• Hearle NCM et al. (2006). Exonic STK11 deletions are not a rare cause of Peutz-Jeghers syndrome. J Med Genet. 43:e15.
• Jang MS et al. (2017). Complete STK11 Deletion and Atypical Symptoms in Peutz-Jeghers Syndrome. Ann Lab Med. 37:462-4.
• Jansen M et al. (2009). LKB1 and AMPK family signaling: the intimate link between cell polarity and energy metabolism. Physiol Rev. 89:777-98.
• Jiang YL et al. (2019). STK11 gene analysis reveals a significant number of splice mutations in Chinese PJS patients. Cancer Genet. 230:47-57.
• Kaluzny A et al. (2012). Organ-sparing surgery of the bilateral testicular large cell calcifying sertoli cell tumor in patient with atypical Peutz-Jeghers syndrome. Int Urol Nephrol. 44:1045-8.
• Kobayashi Y et al. (2014). A tumor of the uterine cervix with a complex histology in a Peutz-Jeghers syndrome patient with genomic deletion of the STK11 exon 1 region. Future Oncol. 10:171-7.
• Lipsa A et al. (2019). Novel germline STK11 variants and breast cancer phenotype identified in an Indian cohort of Peutz-Jeghers syndrome. Hum Mol Genet. 28:1885-93.
• Yang HR et al. (2010). Germline mutation analysis of STK11 gene using direct sequencing and multiplex ligation-dependent probe amplification assay in Korean children with Peutz-Jeghers syndrome. Dig Dis Sci. 55:3458-65.

References

• Borun P et al. (2015). Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz-Jeghers syndrome. Fam Cancer. 14:455-61.
• Chow E et al. (2006). An updated mutation spectrum in an Australian series of PJS patients provides further evidence for only one gene locus. Clin Genet. 70:409-14.
• Ji H et al. (2007). LKB1 modulates lung cancer differentiation and metastasis. Nature. 448:807-10.
• Orellana P et al. (2013). Large deletions and splicing-site mutations in the STK11 gene in Peutz-Jeghers Chilean families. Clin Genet. 83:365-9.
• Wingo SN et al. (2009). Somatic LKB1 mutations promote cervical cancer progression. PLoS One. 4:e5137.