Lab Test

Test Definition Number : 40
Test Definition Name : CALR sequence analysis
Lab Name : OHSU Knight Diagnostics Lab
Lab Test Number of THIS Version : 1020
Lab Test Name : Calreticulin (CALR) Gene Mutations
Status : Active
Expired : No
Updated : 2017-09-21 17:05 EDT

General Attributes

Chromosome Band : 19p13.2
19p13.3
HUGO Gene Name : [CALR] calreticulin
ICD-Oncology Code
(includes WHO classification diagnoses)
:

Infectious Disease Attributes

Agent Category :
Non-virus Genus and Species :
Virus Family, Genus, and Species :

Lab-specific Attributes

Method : Electrophoresis - Capillary
Polymerase Chain Reaction (PCR)
Specimen Source
(for clinical patient care these sources must be validated)
: Blood - Whole Blood
Bone Marrow Aspirate
ICD-10 Code :
Use :
Genetics Category :
SNOMED CT :
LOINC :
Comments : The calcium-binding endoplasmic reticulin chaperone protein Calreticulin (CALR) has recently been shown to be somatically mutated in the majority of patients with a myeloproliferative neoplasm that lack a mutation in the JAK2 gene. In particular, two independent groups (1, 2) have each recently found a variety of insertion or deletion mutations in exon 9 of the calreticulin gene in: 1) ~70% of patients with JAK2-negative essential thrombocythemia (ET), 2) ~60-80% of patients with JAK2-negative primary myelofibrosis, 3) a minority of patients with myelodysplasia (8%), 4) Zero patients with de novo acute myeloid leukemia, chronic myeloid leukemia, lymphoid leukemia, or solid tumors. At the protein level, to date, all of the heterogeneous mutations in CALR each creates the same +1 basepair frameshift mutation that truncates the C-terminal calcium-binding acidic domain of the CALR protein (including the KDEL endoplasmic reticulin retrieval signal) and replaces it with a novel C-terminus (1,2). The availability of a new clinical diagnostic assay for these common exon 9 calreticulin gene mutations, together with the analysis of the JAK2 gene for the common V617F mutation (and to a lesser degree MPL mutations), now allows a specific molecular marker to be identified (and potentially monitored) in the overwhelming majority (>90%) of patients with a myeloproliferative neoplasm. The detection of a CALR gene mutation may aid in the specific diagnosis of a myeloproliferative neoplasm, and help distinguish this clonal disease from a benign reactive process. After the MPN diagnosis is made, the presence of a CALR gene mutation also predicts a more indolent disease course with a lower thrombotic risk and longer overall survival (relative to those with a JAK2 mutation) (1). Although specific targeted therapy for calreticulin-mutated MPN patients has not yet been described, the in vitro expression of this mutation conveys cytokine-independent growth, activated STAT5 signaling, and sensitivity to JAK2 inhibitors (1). The presence of a clonal CALR gene mutation may also allow minimal residual disease to be molecularly monitored during the course of therapy.
Specimen Transport Requirements : 5-10mL of blood or bone marrow (ACD or EDTA) Keep cold during transport, but do not ship on dry ice. Ship the specimen overnight express. Contact Client Services for shipping kit and instructions (855) 535-1522.
Samples Available for Proficiency Test Sample Exchange : Yes

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