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Alternative Name
CLL Targeted Profile
Test Description

The CLL Targeted Profile detects mutations in key genes recurrently mutated in chronic lymphocytic leukemia (CLL). DNA sequence of targeted regions of the ATM, BIRC3, NOTCH1, SF3B1, and TP53 genes is determined using next-generation sequencing (NGS) technology.

Note: This test is available to legacy Genoptix and New York clients only.

Clinical Significance

The clinical course of chronic lymphocytic leukemia (CLL) is heterogenous, and it ranges from very indolent with a nearly normal life expectancy to rapidly progressive leading to early death. Genomic alterations in the TP53, BIRC3, NOTCH1, and SFB31 genes are associated with adverse outcomes, and their presence or absence can improve risk stratification and treatment selection beyond clinical staging and other prognostic biomarkers1-10.

In a study by Rossi, et al; integrated mutational and cytogenetic analysis was able to divide CLL into 4 prognostic subgroups:

  1. high-risk, harboring TP53 and/or BIRC3 abnormalities (10-year survival: 29%);
  2. intermediate-risk, harboring NOTCH1 and/or SF3B1 mutations and/or del11q22-q23 (10-year survival: 37%);
  3. low-risk, harboring trisomy 12 or a normal genetics (10-year survival: 57%); and
  4. very low-risk, harboring del13q14 only, whose 10-year survival (69.3%) did not significantly differ from a matched general population.

This integrated mutational and cytogenetic model independently predicted survival and improved CLL prognostication accuracy compared with cytogenetics (P < .0001)10. Genomic alterations in the ATM gene, which is located on 11q22-q23, are also associated with an adverse outcome, particularly when both ATM mutation and 11q deletion are present11-12. Genomic alterations impacting TP53 function are associated with the worst outcomes, with short treatment-free interval, short median survival, and poor response to chemotherapy. TP53 mutations specifically have been shown to predict poor survival outcomes independent of 17p chromosome status. The NCCN guidelines recommend TP53 sequencing as informative for prognostic and /or therapy determination and other genes such as NOTCH1, SF3B1, and BIRC3 may provide useful prognostic information1.

Specimen Requirements
  • Bone marrow (Preferred): 2-3 mL in EDTA tube
  • Peripheral Blood: 2-3 mL in EDTA tube
  • FFPE Tissue: Paraffin block
  • Unacceptable: Specimens received fixed in alternative fixation methods. Decalcified, frozen or fresh tissue.
Storage and Transportation

Use cold pack for transport, making sure cold pack is not in direct contact with specimen. DO NOT FREEZE.

CPT Code(s)*
New York Approved
Level of Service
Turnaround Time

10-12 Days

  1. National Comprehensive Cancer Network (NCCN) Practice Guidelines in Oncology, Non-Hodgkin’s Lymphomas
  2. Zenz T, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol 2010;28:4473-4479.
  3. Rossi D, et al. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Blood 2014;123:2139-2147.
  4. Rossi, D, et al. Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood 2012; 119:2854-2862.
  5. Oscier DG, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood 2013;121:468-475.
  6. Stilgenbauer S, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood 2014;123:3247-3254.
  7. Rossi D, et al. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 2011;118:6904-6908.
  8. Wang L, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011;365:2497-2506.
  9. Quesada V, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 2011;44:47-52
  10. Rossi D, et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood 2013;121:1403-1412.
  11. Austen B, et al. Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. J Clin Oncol 2007;25:5448-5457.
  12. Skowronska A, et al. Biallelic ATM inactivation significantly reduces survival in patients treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 trial. J Clin Oncol 2012;30:4524-32.

*The CPT codes provided with our test descriptions are based on AMA guidelines and are for informational purposes only. Correct CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.