Peutz-Jeghers AMPLIFIED™
Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disorder characterized by polypsosis, mucocutaneous pigmentation, and a variety of tumors, most commonly gastroesophageal, small bowel, colorectal, and pancreatic. Affected individuals are also at increased risk for developing breast, ovarian, uterine, cervical, testicular, and lung cancer.
PrintPeutz-Jeghers Syndrome (PJS) is an autosomal dominant disorder characterized by polypsosis, mucocutaneous pigmentation, and a variety of tumors, most commonly gastroesophageal, small bowel, colorectal, and pancreatic. Affected individuals are also at increased risk for developing breast, ovarian, uterine, cervical, testicular, and lung cancer.
The Peutz-Jeghers AMPLIFIED™ test includes concurrent Gene Sequence Analysis and gross Deletion/Duplication Analysis of the STK11 gene. Mutations in the STK11 gene have been identified in all individuals with a family history of Peutz-Jeghers Syndrome and 91% of those with a negative family history.
Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disorder characterized by the development of gastrointestinal hamartomatous polyps and melanin hyperpigmentation of the skin and mucous membranes. The gastrointestinal (GI) polyps, while benign, can result in chronic bleeding, secondary anemia, and contribute to recurrent obstruction and intussusceptions, often requiring surgical intervention. In addition to polypsis and mucocutaneous pigmentation, PJS patients are predisposed to a variety of tumors, most commonly gastroesophageal, small bowel, colorectal, and pancreatic.1 With an estimated incidence of 1 in 120,000 births, individuals affected by PJS are also at increased risk for developing breast, ovarian, uterine, cervical, testicular, and lung cancer.2,3 Overall, individuals affected with PJS have an 81% risk of developing cancer by age of 70, with GI and breast cancers being the most common.4,5,6
PJS is caused by mutations in the STK11 gene (previously known as LKB1). Located on chromosome 19p13.3, STK11 is comprised of 10 exons, only nine of which code for the serine threonine protein kinase-11.7 STK11 is a tumor suppressor gene that helps in cell cycle arrest and growth suppression.8 STK11 also interacts with the p53 tumor suppressor to regulate apoptosis. Polyps in PJS have been shown to have reduced numbers of apoptotic cells and lack STK11 protein expression.9 Mutations in STK11 result in a truncated protein that causes an inactivation of kinase domains.10,1
Treatment options are available for disease management, including removal of polyps, as well as preventative screening and standard treatments for the associated cancers. Genetic testing should be considered for symptomatic individuals with a suspected clinical diagnosis of PJS. Testing can identify individuals who are at increased risk of cancers associated with STK11 mutations.1
This Ambry Test: Peutz-Jeghers AMPLIFIED includes concurrent gene sequence analysis and gross deletion/duplication analysis of the STK11 gene. PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-9 of the STK11 gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns and analysis for gross deletions/duplications of the STK11 gene is performed by the Multiplex Ligation-Dependent Probe Amplification (MLPA) kit, developed by MRC Holland. Specific mutation analysis for individual STK11 mutations known to be in the family is also available.
Mutations in STK11 have been identified in nearly all individuals with a family history of PJS, and about 90% of those with a negative family history.11 The Ambry Test: Peutz-Jeghers AMPLIFIED is capable of detecting >99% of identified mutations in STK11.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 2760 | STK11 Gene Sequence Analysis | 83891x1, 83894x9, 83898x8, 83904x16, 83909x16, 83912x1 |
| 2764 | STK11 Deletion / Duplication Analysis | 83891x1, 83894x1, 83900x1, 83901x11, 83909x1, 83912x1 |
| 2766 | STK11 Sequencing and Deletion / Duplication | 83891x1, 83894x9, 83898x8, 83904x17, 83900x1, 83901x11, 83909x16, 83912x2 |
| Technique | Days |
|---|---|
| STK11 Gene Sequence Analysis | 10-21 |
| STK11 Deletion/Duplication Analysis | 7-14 |
| STK11 Sequencing and Deletion / Duplication | 10-21 |
1 Westerman AM et al. Scand J Gastroenterol Suppl. 1999; 230: 64-70.
2 Giardiello FM et al. Gastroenterology. 2000; 119(6): 1447-53.
3 Marignani PA. J Clin Pathol. 2005; 58(1): 15-9.
4 Boardman LA et al. Human Mutation. 2000; 16(1): 23-30.
5 Spigelman AD et al. Gut.1989; 30:1588-1590.
6 Lim W et al. Gastroenterology. 2004; 126:1788-1794.
7 Jenne DE et al. Nat Genet. 1998; 18(1): 38-43.
8 Tiainen M et al. Hum. Mol. Genet. 2002; 11(13): 1497-1504.
9 Karuman P et al. Molecular Cell. 2001; 7(6): 1307-1319.
10 Ylikorkala A et al. Hum Mol Genet. 1999; 8(1): 45-51.
11 Aretz S et al. Human Mutation. 2005;26(6): 513-519.
12 Hemminki A. CLMS. 1999; 55: 735-750.