Intended use: The SALSA MLPA probemix P101 STK11 is an in vitro diagnostic (IVD)
1 or a research use only (RUO) assay for the detection of deletions or duplications in the human
STK11 gene, in order to confirm a potential cause and clinical diagnosis for Peutz-Jeghers syndrome. This assay is for use with human DNA extracted from peripheral blood. This product can also be used for molecular genetic testing of at-risk family members.
Deletions or duplications obtained with the P101 STK11 probemix must be confirmed by another technique. In particular, deletions or duplications detected by only a single probe always require validation by another method. Most defects in the
STK11 gene are small indel-type mutations, none of which will be detected by MLPA. It is therefore recommended to use this SALSA MLPA probemix in combination with sequence analysis of the
STK11 gene. This assay is not intended to be used as a standalone assay for clinical decisions. The results of this test must be interpreted by a clinical molecular geneticist or equivalent.
1Please note that this probemix is for In Vitro Diagnostic use (IVD) in the countries specified at the end of the product description. In all other countries, the product is for Research Use Only (RUO).
Clinical background: 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 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% 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/.
P101-B4 probemix content: This SALSA MLPA P101 STK11 probemix contains 27 probes with amplification products between 150 and 391 nt: 12 probes for the
STK11 gene (one probe for each exon and three probes for exon 1), 3 probes for genes located upstream of
STK11 (
CDC34,
ELANE and
KISS1R), 2 DNA denaturation probes, and 10 reference probes detecting sequences on other chromosomes. The identity of the genes detected by the reference probes is available online (
www.mlpa.com).
This probemix contains nine quality control fragments generating amplification products between 64 and 121 nt: four DNA Quantity Fragments (Q-fragments), two DNA Denaturation Fragments (D-fragments), one benchmark fragment, and one chromosome X and one chromosome Y-specific fragment (see table in the product description). More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at
www.mlpa.com.