CPT Code(s): 81455
Service Code (IU Health):
Ordering Recommendation: Targeted genomics panel for molecular profiling of PCM patients to assess their risk and identify potential targeted therapies relevant to their disease
Synonyms: Multiple myeloma (MM), Kahler disease, myelomatosis
Methodology: Targeted next generation sequencing (NGS)
Performed: Weekly
Reported: 2–6 weeks from the time the laboratory received specimens
None required for whole blood/bone marrow
Tumor sample
Bone Marrow: collect 3-6 mL of bone marrow aspirate in a heparinized syringe and place into sodium heparinized tube for cell sorting.
Fresh sorted CD138+ cells: 500,00 to 1,000,000 cells (1,000,000 preferred) from the collected Bone Marrow aspirate suspended in phosphate buffer saline (PBS) or in cell lysis buffer (Qiagen Lysis Buffer G2).
Non-tumor sample
Saliva (Preferred): collect 2 mL saliva utilizing an Oragene collection device
Blood: collect 1-3 mL in Lavender (EDTA) tubes.
NOTE: blood samples are not accepted for patients with Plasma Cell Leukemia (PCL).
Bone marrow: 3-6 mL of bone marrow aspirate.
Fresh sorted CD138+ cells: ≥1,000,000 cells preferred (minimum accepted is 500,000 cells).
Saliva: ≥2 mL in an Oragene collection tube.
Blood: 1-3 mL of whole blood.
Bone marrow/Sorted CD138+ cells: room temperature and should arrive in laboratory within 24 hours.
Saliva: room temperature.
Blood: room temperature and should arrive in laboratory ≤5 days after collection.
Sorted CD138+ cells: received >24 hours after collection, clotted, or low viability.
Saliva: if evaporated or arrive in the laboratory >1 month after collection.
Blood: if frozen, grossly hemolyzed, clotted, or arrive in the laboratory >5 days after collection.
NOTE: Blood samples form patients with Plasma Cell Leukemia (PCL) are not accepted.
CD138+ cells: 24 hours at room temperature from the time of bone marrow sample collection.
Saliva: for 1 month at room temperature.
Blood: 5 days at room temperature.
N/A
Plasma cell myeloma, also known as multiple myeloma, Kahler disease, and myelomatosis, is the most common primary bone malignancy due to a neoplastic proliferation of monoclonal plasma cells within the bone marrow. The PCM panel includes 224 genes previously published and frequently mutated genes, 56 loci for copy number variation, and 6 loci for detecting recurrent immunoglobulin and MYC translocations. The PCM panel can detect translocations involving the IGH, IGK, IGL and MYC loci, as well as relevant copy number abnormalities (del(1p), gain/amp(1q), del(13q), del(17p), and hyperdiploidy), single nucleotide variants such as base substitutions and small insertions and deletions. The panel has additional probes at known polymorphic SNPs to aid with copy number determination and detect copy number neutral loss of heterozygosity.
The mutational spectrum of PCM has a broad range of driver genes that are recurrently mutated.1-6 These include MAPK/ERK pathway mutations in KRAS (22%), NRAS (18%), and BRAF (8%), as well as the NF-κB pathway mutations in TRAF2 (3%), TRAF3 (6%), CYLD (4%), NFKB2 (1%), and NFKBIA (2%). Other frequently mutated genes include TENT5C (9%), DIS3 (10%), and TP53 (6%).
PCM has an incidence of approximately 2.1/100,000 individuals, with a wide range from 0.54 to 5.3 per 100,00 individuals.7
Positive predictive value (PPV) for base substitution, small insertions and deletions and copy number alterations is >99%. PPV for known gene fusions is >95%.
The PCM panel is designed to detect >99% of clinically relevant single nucleotide variants at ≥ 5% VAF, > 98% of small insertions and deletions in protein-coding exons in the gene panel and > 95% of large copy number alterations and known gene fusions.
Only variants within the targeted genomic regions will be detected. Variants outside the targeted genomic regions will not be detected. Variants that have variant allele fraction (VAF) <5% may not be detected. Tumor content greatly affects the ability to detect copy number changes in samples with less than 20% tumor. For samples with low tumor content, the absence of detectable copy number changes should be interpreted with caution. All results should be interpreted in context of clinical findings, relevant history, and other laboratory data.