Distinct Promoter Methylation Patterns Oflkb1in The Hamartomatous Polyps Of Peutz-Jeghers Syndrome And Its Potential In Gastrointestinal Malignancy Prediction

Background Peutz-Jeghers Syndrome (PJS) is known as a rare inherited polyposis due to the malfunction of serine/threonine kinase geneLKB1. However, not all of PJS patients carryLKB1germline mutation. Previous researches have observed the elevated DNA methylation level in PJS polyps. Nevertheless, the mechanism of such abnormal and its impact on PJS patients remains to be fully described. Results The results proved a significant increase on the methylation level ofLKB1promoter in PJS polyps compared with normal colon biopsies through bisulfite PCR followed by Sanger sequencing. Moreover, the methylation pattern in PJS polyps could be further categorized as three different scenarios: hypermethylated, hemimethylated and hypomethylated pattern. Furthermore, immunohistochemistry of DNMT1/3a/3b suggested the up-regulation of DNMT1 and 3a might participate the epigenetic alternation ofLKB1in PJS polyps. Logistic regression suggested hypomethylatedLKB1promoter in PJS polyps as a risk factor for gastrointestinal malignancies in PJS patients. Conclusions The promoter methylation level ofLKB1gene in PJS polyps is generally elevated compared with normal colon mucosa. Yet not all of PJS polyps carry hypermethylatedLKB1promoter. Hypomethylation in this region has linked to malignant tumors in PJS patients. Given the rarity of PJS, this work together with previous researches, have proved the importance ofLKB1promoter methylation in PJS development and prognosis.