Calreticulin (CALR) Mutation Analysis

CPT: 81219
Updated on 11/10/2017
Print Share

Test Details

Use

The calcium-binding endoplasmic reticulin chaperone protein, calreticulin (CALR), is somatically mutated in approximately 70% of patients with JAK2-negative essential thrombocythemia (ET) and 60% to 88% of patients with JAK2-negative primary myelofibrosis (PMF). Only a minority of patients (approximately 8%) with myelodysplasia have mutations in CALR gene. CALR mutations are rarely detected in patients with de novo acute myeloid leukemia, chronic myelogenous leukemia, lymphoid leukemia, or solid tumors. CALR mutations are not detected in polycythemia and generally appear to be mutually exclusive with JAK2 mutations and MPL mutations.

The majority of mutational changes involve a variety of insertion or deletion mutations in exon 9 of the calreticulin gene: approximately 53% of all CALR mutations are a 52 bp deletion (type-1) while the second most prevalent mutation (approximately 32%) contains a 5 bp insertion (type-2). Other mutations (non-type 1 or type 2) are seen in a small minority of cases. CALR mutations in PMF tend to be associated with a favorable prognosis compared to JAK2V617F mutations, whereas primary myelofibrosis negative for CALR, JAK2V617F and MPL mutations (so-called triple negative) is associated with a poor prognosis and shorter survival.

The detection of a CALR gene mutation aids in the specific diagnosis of a myeloproliferative neoplasm, and helps distinguish this clonal disease from a benign reactive process.

The calcium-binding endoplasmic reticulin chaperone protein, calreticulin (CALR), is somatically mutated in approximately 70% of patients with JAK2-negative essential thrombocythemia (ET) and 60% to 88% of patients with JAK2-negative primary myelofibrosis (PMF). Only a minority of patients (approximately 8%) with myelodysplasia has mutations in CALR gene. CALR mutations are rarely detected in patients with de novo acute myeloid leukemia, chronic myelogenous leukemia, lymphoid leukemia, or solid tumors. CALR mutations are not detected in polycythemia and generally appear to be mutually exclusive with JAK2 mutations and MPL mutations.

The calcium-binding endoplasmic reticulin chaperone protein, calreticulin (CALR), is somatically mutated in approximately 70% of patients with JAK2-negative essential thrombocythemia (ET) and 60% to 88% of patients with JAK2-negative primary myelofibrosis (PMF). Only a minority of patients (approximately 8%) with myelodysplasia have mutations in CALR gene. CALR mutations are rarely detected in patients with de novo acute myeloid leukemia, chronic myelogenous leukemia, lymphoid leukemia, or solid tumors. CALR mutations are not detected in polycythemia and generally appear to be mutually exclusive with JAK2 mutations and MPL mutations.

The majority of mutational changes involve a variety of insertion or deletion mutations in exon 9 of the calreticulin gene: approximately 53% of all CALR mutations are a 52 bp deletion (type-1) while the second most prevalent mutation (approximately 32%) contains a 5 bp insertion (type-2). Other mutations (non-type 1 or type 2) are seen in a small minority of cases. CALR mutations in PMF tend to be associated with a favorable prognosis compared to JAK2V617F mutations, whereas primary myelofibrosis negative for CALR, JAK2V617F and MPL mutations (so-called triple negative) is associated with a poor prognosis and shorter survival.

The detection of a CALR gene mutation aids in the specific diagnosis of a myeloproliferative neoplasm, and helps distinguish this clonal disease from a benign reactive process.

Limitations

This PCR assay is capable of detecting a mutant cell population with a sensitivity of 5 mutant cells per 100 normal cells. A negative result does not exclude the presence of a myeloproliferative disorder or other neoplastic process.

Methodology

Polymerase chain reaction (PCR); capillary electrophoresis

Specimen Requirements

Specimen

Whole blood or bone marrow

Volume

3 to 5 mL whole blood or 1 to 2 mL bone marrow

Minimum Volume

3 mL whole blood or 1 mL bone marrow

Container

Lavender-top (EDTA) tube or green-top (sodium heparin) tube

Collection

Ship specimen at room temperature. Specimen should arrive in the laboratory within 48 hours of collection. If specimen is to be stored prior to shipment, store at 2°C to 8°C. Indicate date and time of collection on the test request form.

Storage Instructions

Refrigerate. Stable for 72 hours at room temperature or refrigerated.

Causes for Rejection

Sample greater than 72 hours old; clotted blood

Clinical Information

Special Instructions

Please direct any questions regarding this test to customer service at 800-345-4363.

References

Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013 Dec; 369(25):2379-2390. 24325356
Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013 Dec; 369(25):2391-2405. 24325359

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
489450 CALR Mutation Analysis 489451 CALR Mutation Detection Result 77174-1
489450 CALR Mutation Analysis 489461 Background: N/A
489450 CALR Mutation Analysis 489453 Methodology: 49549-9
489450 CALR Mutation Analysis 489454 References: 75608-0
489450 CALR Mutation Analysis 489449 Director Review: 72486-4
489450 CALR Mutation Analysis 489455 CALR Mutation Analysis N/A

For Providers

Please login to order a test.

 

© 2017  Laboratory Corporation of America® Holdings and Lexi-Comp Inc. All Rights Reserved.

CPT Statement/Profile Statement

The LOINC® codes are copyright © 1994-2017, Regenstrief Institute, Inc. and the Logical Observation Identifiers Names and Codes (LOINC) Committee. Permission is granted in perpetuity, without payment of license fees or royalties, to use, copy, or distribute the LOINC® codes for any commercial or non-commercial purpose, subject to the terms under the license agreement found at https://loinc.org/license/. Additional information regarding LOINC® codes can be found at LOINC.org, including the LOINC Manual, which can be downloaded at LOINC.org/downloads/files/LOINCManual.pdf