STK11

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  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Alias

LKB1; PJS; hLKB1

Associated disorders

The STK11 gene is associated with autosomal dominant Peutz-Jeghers syndrome (PJS) (MedGen UID: 18404).

The STK11 gene encodes a tumor suppressor serine/threonine protein kinase that controls the activity of AMP-activated protein kinase family members, thereby playing a role in various processes such as regulating cell division, cell metabolism, cell polarization, apoptosis and DNA damage response.

STK11 – Peutz-Jeghers syndrome
MedGen UID: 18404

Clinical condition
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. Mucocutaneous hyperpigmentation causes freckling around the mouth, eyes, nose, and perianal area and typically becomes more pronounced in early childhood, later fading in puberty and adulthood. Hyperpigmentation is also commonly found on the fingers (PMID: 20301443).

PJS is associated with the development of benign hamartomas that form in the gastrointestinal tract. Approximately 70%-90% of affected individuals have GI hamartomas in the small intestine; however, such polyps may be present anywhere along the GI tract as well as in the urinary tract, gall bladder, uterus and respiratory tract (PMID: 9429144, 20301443).

Cancer risks associated with PJS include (PMID: 20051941, 16707622, NCCN Genetic/Familial High-Risk Assessment: Colorectal. Version 2.2016):

  • breast cancer, 45%-50%
  • colorectal cancer, 39%
  • pancreatic cancer, 11%-36%
  • gastric cancer, 29%
  • ovarian cancer, 18%-21%
  • lung cancer, 15%-17%
  • small bowel cancer, 13%
  • duodenal cancer, 13%
  • adenoma malignum of the uterine cervix, 10%
  • uterine cancer, 9%
  • testes, rare

Individuals with PJS are at risk for gonadal tumors that often have distinctive pathology. Males are at risk for lesions with features intermediate between testicular sex cord with annular tubules (SCTATs) and large cell calcifying Sertoli cell tumors (PMID: 15502809). These may occur in prepubertal boys, causing sexual precocity and gynecomastia (PMID: 15502809, 16707622). Females may develop ovarian SCTATs, mucinous tumors of the ovaries and fallopian tubes, and adenoma malignum of the cervix (PMID: 15502809, 16707622). Pathologically, SCTAT can resemble both granulosa cell tumors and Sertoli cell tumors. In PJS, SCTAT are usually multifocal, bilateral, small, and calcified with a typically benign course (PMID: 15502809).

Gene information
STK11 is a tumor suppressor gene that encodes serine/threonine kinase 11. This enzyme plays a role in various processes such as cell metabolism, cell polarity, apoptosis, and DNA damage response (UniProtKB – Q15831 (STK11_HUMAN); http://www.uniprot.org/uniprot/Q15831. Accessed January 2017, National Library of Medicine. Genetics Home Reference. STK11. http://ghr.nlm.nih.gov/gene/STK11. Accessed January 2017).

Inheritance
PJS has has autosomal dominant inheritance. This means that an individual with a pathogenic variant has a 50% chance of passing the condition on to their offspring. With this result, it is now possible to identify at-risk relatives who can pursue testing for this specific familial variant. While most cases are inherited from a parent, some occur spontaneously. This means that an individual with a pathogenic variant can have parents who do not have it. However, that individual now has a 50% risk of passing it on to offspring.

Management
Due to the complexity of managing individuals with PJS, it is recommended that affected individuals seek care through a multidisciplinary clinic with experience treating this condition. Management guidelines for individuals with pathogenic STK11 variants have been developed. The National Comprehensive Cancer Network® (NCCN®) suggests the following (NCCN. Genetic/Familial High-Risk Assessment: Colorectal. Version 2.2016):

For females:

  • clinical breast exams every 6 months beginning at age 25
  • annual mammograms and breast MRIs with contrast beginning at age 25
  • pelvic exams and Pap smears annually beginning at 18 to 20 years of age
  • consider transvaginal ultrasound beginning at 18 to 20 years of age

For males:

  • annual testicular exam and observation for feminizing changes beginning at 10 years of age

For males and females:

  • colonoscopy every 2-3 years beginning at approximately age 18
  • upper endoscopy every 2-3 years beginning at approximately age 18
  • baseline small bowel visualization via CT or MRI enterography at approximately 8-10 years of age with follow-up intervals based on findings
  • beginning at approximately age 18, screening should be performed every 2-3 years; however, this may be individualized
  • MRI cholangiopancreatography or endoscopic ultrasound every 1-2 years beginning at approximately 30 to 35 years of age
  • education regarding the signs and symptoms of lung cancer and discuss smoking cessation, if applicable

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors including personal medical history, family history as well as available genetic information that may result in a personalized plan for cancer prevention and surveillance.

It is advantageous to know if a STK11 pathogenic variant is present. At-risk relatives can be identified, allowing pursuit of a diagnostic evaluation. In addition, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant STK11 data is likely to become available in the near future. Awareness of this cancer predisposition allows patients and their providers to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information, inform at-risk family members, and diligently follow condition-specific screening protocols.

An individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors including personal medical history, family history as well as available genetic information that may result in a personalized plan for cancer prevention and surveillance.

It is advantageous to know if a STK11 pathogenic variant is present. At-risk relatives can be identified, allowing pursuit of a diagnostic evaluation. In addition, the available information regarding hereditary cancer susceptibility genes is constantly evolving and more clinically relevant STK11 data is likely to become available in the near future. Awareness of this cancer predisposition allows patients and their providers to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information, inform at-risk family members, and diligently follow condition-specific screening protocols.

Review date: January 2017

Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology
(NCCN Guidelines®) for Genetic/Familial High-Risk Assessment: Colorectal V.2.2016. © National Comprehensive Cancer Network, Inc 2016. All rights
reserved. Accessed 9/26/16. To view the most recent and complete version of the guideline, go online to NCCN.org. National Comprehensive Cancer Network®, NCCN®, NCCN Guidelines®, and all other NCCN content are trademarks owned by the National Comprehensive Cancer Network, Inc.

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