From the Guidelines
STK11 mutation is associated with Peutz-Jeghers syndrome (PJS), a rare autosomal dominant genetic disorder characterized by the development of hamartomatous polyps in the gastrointestinal tract and distinctive mucocutaneous pigmentation. The STK11 gene, also known as LKB1, is a tumor suppressor gene that encodes a serine/threonine kinase involved in cell polarity and energy metabolism regulation 1. When mutated, it disrupts normal cellular functions, leading to polyp formation and increased cancer susceptibility. Patients with PJS have an increased risk of developing various cancers, including gastrointestinal, breast, ovarian, and pancreatic cancers. Key features of PJS include:
- Hamartomatous polyps in the gastrointestinal tract
- Mucocutaneous melanin pigmentation
- Increased risk of gastrointestinal and nongastrointestinal tumors
- Autosomal dominant inheritance pattern Management of PJS involves regular surveillance with endoscopic procedures starting in childhood or adolescence, breast cancer screening, and monitoring for other associated malignancies, as recommended by the NCCN guidelines 1. Genetic counseling is also recommended for affected individuals and their families to understand inheritance patterns and cancer risks. The most recent guidelines from the NCCN recommend referral to a specialized team and participation in available clinical trials for patients who meet clinical criteria for PJS or have a pathogenic or likely pathogenic variant in STK11 1. Additionally, the guidelines recommend annual pelvic examination and Papanicolaou test starting at around ages 18 to 20 years, as well as annual pelvic ultrasound, to monitor for gynecologic cancer. Overall, the management of PJS requires a multidisciplinary approach, including genetic counseling, surveillance, and screening for associated malignancies, to reduce the risk of morbidity and mortality associated with this condition 1.
From the Research
Syndrome Indicated by STK11 Mutation
The syndrome indicated by STK11 mutation is Peutz-Jeghers syndrome (PJS), a rare autosomal dominant polyposis syndrome characterized by gastrointestinal hamartomatous polyps, mucocutaneous hyperpigmentation, and an increased risk of cancer 2, 3, 4, 5, 6.
Key Characteristics of Peutz-Jeghers Syndrome
- Gastrointestinal hamartomatous polyps
- Mucocutaneous hyperpigmentation
- Increased risk of cancer
- Autosomal dominant inheritance pattern
STK11 Gene Mutations in Peutz-Jeghers Syndrome
- Truncating mutations in the STK11 gene are associated with more severe complications, including more polyps, surgical interventions, and cancers 2, 3
- Non-truncating mutations may also be associated with an increased risk of cancer, although the risk may be lower than with truncating mutations 2
- Specific mutations in the STK11 gene, such as those affecting protein kinase domain XI, may be associated with a higher risk of dysplastic polyps and cancer 4