Peutz-Jeghers-syndrome is an autosomal dominantly inherited disorder that is characterized by the combination of:
Synonyms
Although Peutz-Jeghers syndrome is autosomal dominantly inherited, a large number of sporadic cases (possibly new mutations) occur. The disease is equally distributed between the sexes and the races. The clinical problems are bleeding, pain and intussuception caused by the intestinal hamartosis and the increased risk for various tumors. The majority of cases is caused by mutations in a gene called STK11 or LKB1 on chromosome 19p13.3, however, in some cases this gene was found not to be mutated. It seems therefore probable that mutations in a second (yet unknown) gene may also cause PJS. Since the syndrome is extremely rare, the overall rate of occurrence is not known.
Pathogenesis
Most cases of PJS are caused by a mutation in the STK11 or LKB1 gene. The gene product has a strong homology to the serine-threonine protein kinase XEEK1 from Xenopus. Recent results showed that the STK11/LKB1 protein is nuclear as well as cytoplasmic. It has a growth-suppressing activity which is mediated by a G(1) cell-cycle arrest.
The gene has been investigated in many different sporadic tumors like colorectal, gastric, testicular, pancreatic, ovarian, and breast cancer, in malignant melanoma as well as in different tumor cell lines. Mutations of the STK11/LKB1 gene were rare in these tumors, suggesting a minor role in the evolvement of sporadic tumors.
Loss of heterozygosity of the wild-type allele has been demonstrated in the hamartomatous polyps and in 70% of the malignant tumors investigated from PJS patients.
In a minority of PJS cases no STK11/LKB1 mutation has been found, suggesting a second gene, responsible for the cases of PJS.
Sources : Encyclopedic Reference of Cancer (Springer-Verlag) 2001
- Lentiginosis, i.e. typical pigmented lesions.
- Hamartomatous polyposis that occurs mainly in the small intestine but also in the colon and the stomach. Extraintestinal hamartomas are rare; possible localizations include the gallbladder, the urinary bladder, the heart, and the respiratory tract.
- Increased risk for various types of cancer (e.g. Pancreas, gastrointestinal tract, bilateral breast cancer, rare gynecological tumors).
Synonyms
- Peutz-Touraine-syndrome
- hereditary hamartosis Peutz-Jeghers
- Hutchinson-Weber-Peutz-syndrome
- Lentiginosis polyposa Peutz
- PJS
Although Peutz-Jeghers syndrome is autosomal dominantly inherited, a large number of sporadic cases (possibly new mutations) occur. The disease is equally distributed between the sexes and the races. The clinical problems are bleeding, pain and intussuception caused by the intestinal hamartosis and the increased risk for various tumors. The majority of cases is caused by mutations in a gene called STK11 or LKB1 on chromosome 19p13.3, however, in some cases this gene was found not to be mutated. It seems therefore probable that mutations in a second (yet unknown) gene may also cause PJS. Since the syndrome is extremely rare, the overall rate of occurrence is not known.
Pathogenesis
Most cases of PJS are caused by a mutation in the STK11 or LKB1 gene. The gene product has a strong homology to the serine-threonine protein kinase XEEK1 from Xenopus. Recent results showed that the STK11/LKB1 protein is nuclear as well as cytoplasmic. It has a growth-suppressing activity which is mediated by a G(1) cell-cycle arrest.
The gene has been investigated in many different sporadic tumors like colorectal, gastric, testicular, pancreatic, ovarian, and breast cancer, in malignant melanoma as well as in different tumor cell lines. Mutations of the STK11/LKB1 gene were rare in these tumors, suggesting a minor role in the evolvement of sporadic tumors.
Loss of heterozygosity of the wild-type allele has been demonstrated in the hamartomatous polyps and in 70% of the malignant tumors investigated from PJS patients.
In a minority of PJS cases no STK11/LKB1 mutation has been found, suggesting a second gene, responsible for the cases of PJS.
Sources : Encyclopedic Reference of Cancer (Springer-Verlag) 2001