Invitae Peutz-Jeghers Syndrome Test


Test description

This test analyzes the STK11 gene, which is associated with Peutz-Jeghers syndrome (PJS). PJS is a cancer predisposition syndrome characterized by mucocutaneous pigmentation, numerous precancerous polyps in the gastrointestinal tract, and an increased risk of developing a variety of cancers.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (1 gene)


Alternative tests to consider

Peutz-Jeghers syndrome can also be ordered as part of a broader panel to test for different types of hereditary cancer, including breast and ovarian, colon, and pancreatic cancers. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered for no additional charge.

Peutz-Jeghers syndrome (PJS)

Peutz-Jeghers syndrome (PJS) is a cancer predisposition syndrome characterized by the development of numerous precancerous polyps in the gastrointestinal tract and an increased risk of developing a wide variety of cancers, including colorectal, pancreatic, stomach, small bowel, and lung. Women with PJS also have increased lifetime risk of breast, ovarian, cervical, and uterine cancers. PJS is characterized by hyperpigmentation of the mucous membranes, which causes freckling around the mouth, eyes, nose, and perianal area. Hyperpigmentation is also common on the fingers.

Essentially everyone with a pathogenic STK11 variant will manifest symptoms of PJS. PJS is also highly variable, meaning individuals with the same condition may present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant.

Cancer typeLifetime risk
Breast 45%-50%
Colorectal 39%
Gastric 29%
Ovarian 18%-21%
Pancreatic 11%-36%
Lung 15%-17%
Duodenal 13%
Cervical (adenoma malignum) 10%
Uterine 9%

Approximately 80%-94% of individuals with a clinical diagnosis of PJS have an identifiable pathogenic variant in the STK11 gene.

PJS is inherited in an autosomal dominant pattern. Approximately 45% of affected individuals have no family history of PJS, but the proportion of cases due to spontaneous de novo mutations is unclear.

The prevalence of PJS is estimated to be 1 in 50,000 to 1 in 200,000 individuals.

Analysis of the STK11 gene may be considered in individuals with the following features:

  • two or more histologically confirmed PJS-type hamartomatous polyps
  • any number of PJS-type polyps detected in one individual who has a family history of PJS in one or more close relatives
  • characteristic mucocutaneous pigmentation in an individual who has a family history of PJS in one or more close relatives
  • any number of PJS-type polyps in an individual who also has characteristic mucocutaneous pigmentation

Clinical diagnostic criteria for PJS have also been proposed:

  1. Beggs, AD, et al. Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010; 59(7):975-86. doi: 10.1136/gut.2009.198499. PMID: 20581245
  2. Hampel, H, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet. Med. 2015; 17(1):70-87. doi: 10.1038/gim.2014.147. PMID: 25394175
  3. Higham, P, et al. Medical management update: Peutz Jeghers syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010; 109(1):5-11. doi: 10.1016/j.tripleo.2009.08.022. PMID: 20123375
  4. McGarrity, TJ, et al. Peutz-Jeghers Syndrome. 2001 Feb 23. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: PMID: 20301443
  5. National Comprehensive Cancer Network, Clinical practice guidelines in oncology. Genetic/Familial High Risk Assessment: Colorectal. Accessed September 2015.
  6. Syngal, S, et al. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am. J. Gastroenterol. 2015; 110(2):223-62; quiz 263. doi: 10.1038/ajg.2014.435. PMID: 25645574
  7. van, Lier, MG, et al. High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance recommendations. Am. J. Gastroenterol. 2010; 105(6):1258-64; author reply 1265. doi: 10.1038/ajg.2009.725. PMID: 20051941

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
STK11 NM_000455.4