Piebaldism and Familial Gastrointestinal Stromal Tumors (GISTs) via the KIT Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4697 KIT 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4697KIT81479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Hannah Cox, PhD

Clinical Features and Genetics

Clinical Features

Piebaldism is caused by inactivating pathogenic variants in KIT, while neoplasms (GISTs, GCTs, AML, CML and lymphomas) are caused by activating, or gain-of-function, pathogenic variants (Akin and Metcalf 2004). KIT encodes a transmembrane receptor tyrosine kinase that responds to the Stem Cell Factor (SCF) ligand. Kit is expressed on the surface of several different cell types, including melanocytes, gastrointestinal pacemaker cells, hematopoietic progenitor cells, mast cells and germ cells. In melanocytes, Kit signaling is required for migration from the embryonic neural crest; loss of Kit function results in the absence of melanocytes in midline patches of hair and skin. In other cells, signaling through the SCF/c-kit pathway promotes proliferation and survival; constitutive activation of Kit in these cells causes excessive proliferation, malignancy and metastasis. Loss-of-function variants are found throughout all 21 exons of the KIT gene, whereas activating variants appear to be clustered in exons 2, 8, 9, 11, 13 and 17 (Heinrich et al. 2002). Importantly, the selective Kit inhibitor Gleevec (Novartis Pharmaceuticals, East Hanover, NJ) is a very effective treatment for KIT-dependent neoplasms (Tuveson et al. 2001). However, a few activating variants, such as D816V, have been shown to be insensitive to Gleevec (Miettinen et al. 2002). As a result, identifying the causative variant in these neoplasms is critical for determining the most effective mode of treatment.

Genetics

Pathogenic variants in the c-kit proto-oncogene (KIT) cause a variety of disorders, including piebaldism, gastrointestinal stromal tumors (GISTs), germ cell tumors (GCTs) and hematopoietic neoplasms such as acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and malignant lymphoma (Akin and Metcalfe 2004). Piebaldism is an autosomal dominant disorder characterized by patches of skin and hair that entirely lack pigment (Murakami et al. 2004). These white patches are mainly found on the scalp and forehead, resulting in a distinctive white forelock trait. Gastrointestinal stromal tumors, or GISTs, are rare mesenchymal tumors that specifically express the Kit protein and originate in the gastrointestinal (GI) tract or abdomen (Miettinen et al. 2002). In most cases, GISTs spontaneously arise due to somatic pathogenic variants of the KIT gene. However, families with germline pathogenic variants in the KIT gene have also been described (Isozaki et al. 2000; Maeyama et al. 2001). In these families, inheritance of heterozygous KIT variants leads to cutaneous hyperpigmentation and development of multiple GISTs.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to detect a loss-of-function pathogenic variant in nearly all patients with piebaldism (Syrris et al. 2002). The clinical sensitivity of germline pathogenic variants in KIT from individuals with GIST is considered to be low, but at least 16 variants have been reported in several families with multiple occurrences of GIST (Bachet et al. 2013).

The clinical sensitivity for detection of large deletions and duplications is not known; however, gross deletions have been reported for Piebaldism (Ezoe et al. 1995).

Testing Strategy

This test provides full coverage of all coding exons of the KIT gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with piebaldism or suspicion of familial GISTs.

This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue. This test is also not recommended for patients with mastocytosis (Valent et al. 2007).

Gene

Official Gene Symbol OMIM ID
KIT 164920
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Gastrointestinal Stromal Tumors AD 606764
Partial Albinism AD 172800

Related Tests

Name
Familial Gastrointestinal Stromal Tumors (GISTs) via the PDGFRA Gene
Waardenburg Syndrome Type IID via the SNAI2 Gene

Citations

  • Akin C., Metcalfe D.D. 2004. The Journal of Allergy and Clinical Immunology. 114: 13-9; quiz 20. PubMed ID: 15241338
  • Bachet J.B. et al. 2013. European Journal of Cancer (oxford, England : 1990). 49: 2531-41. PubMed ID: 23648119
  • Ezoe K. et al. 1995. American Journal of Human Genetics. 56: 58-66. PubMed ID: 7529964
  • Heinrich M.C. et al. 2002. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 20: 1692-703. PubMed ID: 11896121
  • Isozaki K. et al. 2000. The American Journal of Pathology. 157: 1581-5. PubMed ID: 11073817
  • Maeyama H. et al. 2001. Gastroenterology. 120: 210-5. PubMed ID: 11208730
  • Miettinen M. et al. 2002. European Journal of Cancer (oxford, England : 1990). 38 Suppl 5: S39-51. PubMed ID: 12528772
  • Murakami T. et al. 2004. Journal of Dermatological Science. 35: 29-33. PubMed ID: 15194144
  • Syrris P. et al. 2002. Human Mutation. 20: 234. PubMed ID: 12204004
  • Tuveson D.A. et al. 2001. Oncogene. 20: 5054-8. PubMed ID: 11526490
  • Valent P. et al. 2007. European Journal of Clinical Investigation. 37: 435–453. PubMed ID: 17537151

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
×
Copy Text to Clipboard
×