Peutz-Jeghers syndrome and cancer linked by LKB1

Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder, characterized by mucocutaneous pigmentations, hamartomas presenting as gastrointestinal polyps, and an increased cancer risk

Omineca Herald, May, 23, 1924

Background: LKB1 mutations are the underlying genetic abnormality causing Peutz-Jeghers syndrome (PJS) and are a potential target for everolimus. In this phase II study, the efficacy of everolimus on polyp and tumor growth in PJS patients was investigated. Methods: 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. Treatment in both groups was oral everolimus, 10 mg daily. Response rates were primary endpoints for both cohorts. Results: Between October 2011 and April 2016, only two patients were enrolled, one in each cohort. A 49-year-old patient with advanced pancreatic cancer in cohort 1 was progressive after 2 months. A 52-year-old male patient in cohort 2 experienced severe toxicity and refused treatment after 4 months, even though endoscopy suggested stabilization of polyps. Adverse

[Peutz-Jeghers syndrome].

Peutz-Jeghers syndrome is a rare, autosomal dominant inherited disorder, which is characterized by mucocutaneous pigmentations, gastrointestinal polyposis and an increased risk of cancer. It is caused by germline mutations in the LKB1 tumour suppressor gene, as a result of which hamartomatous polyps can develop already at an early age, which may cause various complications, including abdominal pain, anaemia, and acute intestinal obstruction. Patients have an increased risk of developing cancer, in the gastroinstestinal tract and in other organs. As a result of the risk of complications related to the hamartomatous polyps and the increased risk of cancer, the medical management mainly consists of surveillance. Upper and lower endoscopies are recommended for surveillance, the small bowel should be investigated with magnetic resonance imaging and regular inspection of the pancreas with imaging techniques is recommended. Women are advised to seek regular breast- and gynaecological screening from an early age. The pathogenesis of hamartomas and carcinomas is unclear. More insight into the molecular background might lead to targeted medicinal therapies for patients with this syndrome

Pancreatic cancer risk in Peutz-Jeghers syndrome patients: A large cohort study and implications for surveillance

Background Although Peutz-Jeghers syndrome (PJS) is known to be associated with pancreatic cancer (PC), estimates of this risk differ widely. This hampers counselling of patients and implementation of surveillance strategies. We therefore aimed to determine the PC risk in a large cohort of Dutch PJS patients. Methods PJS was defined by diagnostic criteria recommended by the WHO, a proven LKB1 mutation, or both. All patients with a presumptive diagnosis of pancreatic, ampullary or distal bile duct cancer were identified. Cases were reviewed clinically, radiologically and immunohistochemically. Cumulative PC risks were calculated by Kaplan-Meier analysis and relative risks by Poisson regression analysis. Results We included 144 PJS patients (49% ma