The substitutions of single amino acids in highly conserved regions of the STK11 protein are associated with Peutz-Jeghers syndrome (PJS), which is an autosomal dominant inherited disorder.
Whole-exome and Sanger sequencing identified somatic mutations in STK11 (a causative gene of Peutz-Jegher syndrome; n=3), CTNNB1 (n=2), and APC (a gene of familial adenomatous polyposis; n=1) in ICPNs, while those alterations were exceptional in papillary and nonpapillary GBCs.
Peutz-Jeghers syndrome (PJS) is a Mendelian disease, whose causative gene is STK11, mainly characterized by gastrointestinal polyposis and increased cancer risk.
This is the first report showing ER positivity in breast cancer in carriers of STK11 variants and needs confirmation in a larger pooled cohort of PJS associated breast cancers.
The combination of direct sequencing and multiple ligation-dependent probe amplification (MLPA) has resulted in an 80% detection rate of serine/threonine kinase 11 (STK11) gene mutations in Peutz-Jeghers syndrome (PJS); however, this rate varies in different ethnicities.
This finding of mosaicism was several years after initial investigations failed to identify the same STK11 mutation in this woman whose son was diagnosed with PJS at a young age.
Although the main clinical features of pediatric PJS were similar to those of PJS cases in adults, a high frequency of STK11 de novo mutations were encountered in our population of patients with PJS.
Germline mutations in the STK11 gene (encoding LKB1) are the cause of the Peutz-Jeghers syndrome, which is characterized by benign polyps in the intestine and a higher risk for the patients to develop intestinal and extraintestinal tumors.
Our results identify LKB1-mediated inflammation as a tissue-extrinsic regulator of intestinal polyposis in PJS, suggesting possible therapeutic approaches by targeting deregulated inflammation in this disease.
Peutz-Jeghers syndrome (PJS) is a rare hereditary disease caused by mutations in serine threonine kinase 11 (<i>STK11</i>) and characterized by an increased risk of developing cancer.
In this study, peripheral blood genomic DNA samples from a Chinese PJS family with a high cancer risk were examined for STK11 mutations using Sanger sequencing and MLPA analysis.
Previous work has implicated LKB1 - the causative gene in the autosomal dominant, cancer pre-disposing disease called Peutz-Jeghers Syndrome (PJS), and its downstream target AMPK, in the establishment of germline stem cell (GSC) quiescence during the dauer stage.
The present study reports the spectrum of STK11 mutations in eight families with clinical diagnosis of PJS, summarizes the clinical characteristics of sixteen mutation carriers and launches a National Registry for PJS in Greece.
The liver kinase B1 (LKB1) gene is a tumor suppressor associated with the hereditary Peutz-Jeghers syndrome and frequently mutated in non-small cell lung cancer and in cervical cancer.
These data indicate that IL-11-mediated induction of JAK/STAT3 is critical in gastrointestinal tumorigenesis following Lkb1 mutations and suggest that targeting this pathway has therapeutic potential in Peutz-Jeghers syndrome.
Adult patients with a proven LKB1 mutation and who were suitable for everolimus treatment were included in two different PJS cohorts: (a) patients with unresectable malignancies and (b) patients with high-risk polyps.