Tests by Technology

Genoptix’s sole focus is to provide quality diagnostic services for community hematologists/oncologists. We understand that accurate diagnosis, treatment, and monitoring are keys to effective patient management.

Our deep level of expertise in this specialty area of cancer allows us to provide physicians and their patients with the most recent technologies that provide the most reliable test results.


Preparation of blood smears and/or bone marrow core/clot and smears for staining and identification of number and morphology of cells. Morphologic analysis includes immunohistochemistry and special stains, such as iron and reticulin stains.

Immunohistochemistry: CD20 Confirms Presence of B-cell Infiltrate Special Stain: Widespread Reticulin, Fibrosis

Flow Cytometry Tests

Intelligent Flow Profile Flow cytometric phenotyping for hematologic malignancies. Uses rational marker selection for efficient flow analysis of up to 43 antibodies.

CLL Diagnostic/Prognostic Profile Includes identification of leukemic B-cells by establishing clonality and assessing prognostic indicators. Diagnostic confirmation of suspected CLL and prognostic insight for tumor aggressiveness and clinical behavior.

CLL Monitoring/Minimal Residual Disease (MRD) Profile Detects the presence of MRD (down to .01%) post-treatment for CLL using the international standardized approach. Assesses effectiveness of treatment and provides prognostic information for Progression-Free Survival (PFS) and Overall Survival (OS).

Paroxysmal Nocturnal Hemoglobinuria (PNH) Evaluation Measurement of glycosyl-phosphatidylinositol (GPI) linkage and determination of reduction or loss of specific antigens on monocytes, granulocytes, and lymphocytes. Immunophenotyping specifically for suspected PNH.

DNA Ploidy and S-Phase Cell Cycle Analysis for Confirmed Plasma Cell Dyscrasia Measurement of DNA ploidy and percent of cells in S-phase for cell proliferation along with other relevant markers. Information to help determine prognosis and assist in management of plasma-cell dyscrasias.

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Cytogenetics with Reflex to Fluorescence in situ Hybridization (FISH) Metaphase analysis of chromosomal abnormalities through traditional banding identification, and further reflex to interphase FISH for chromosome-region-specific labeling as needed. Inclusion of karyotype image with key findings identified and photomicrographs of relevant FISH probes.

Cytogenetics-Karyotyping Only Traditional G-banding for metaphase analysis. Detection of chromosomal gains and/or losses, as well as deletions, inversions, or translocations specific to hematopoietic malignancies.

Normal Male Karyotype Abnormal Male Karyotype: Unbalanced Translocation
Between Chromosomes 1q and 19p

Fluorescence in situ Hybridization (FISH) Gene-specific targeting of chromosomal abnormalities in leukemias and myeloid disorders. Profiles available for CLL, MM, MDS, MPD, AML, and ALL as well as individual probes for specific subsets of lymphomas and leukemias, myeloproliferative neoplasms, and bone marrow transplantation.

EGFR Amplification Analysis Analysis of the number of epithelial growth factor receptors (EGFRs) as an indicator of a favorable response to EGFR inhibitors such as cetuximab and erlotinib. EGFR amplification analysis is helpful in the management of lung and other cancers.

Medicare Local Coverage Determination Information

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Molecular Tests

DNA Sequencing The Genoptix team of molecular biologists also applies their expertise to DNA sequencing analysis. DNA sequencing determines the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a specific region of a patient’s DNA. Specific mutations, and the extent of mutation, in the DNA sequence can often times provide diagnostic and prognostic information with regard to leukemias and lymphomas. With COMPASS, a dedicated Genoptix hematopathologist correlates DNA sequencing results with morphology, flow cytometry, cytogenetics, FISH, and molecular results for a patient-specific diagnosis.

IgVH Somatic Hypermutation Analysis Identification of the % mutation in the IgH gene V region compared with the native germline provides prognostic information in patients with confirmed CLL. IgH gene mutations >2% indicate a favorable prognosis, while IgH gene mutations ≤2% indicate a less favorable prognosis. This test is especially helpful as prognoses of CLL patients vary dramatically. 

bcr/abl t(9;22) Quantitative GenoTRACE® Assay for CML Real-time PCR for detection of t(9;22) and quantitation in chronic mylogenous leukemia (CML). Offers exceptional sensitivity (1:10,000 cells) for serial monitoring of residual disease and molecular response to treatment.

Sample bcr/abl Graph

JAK2 (Janus Kinase 2) Quantitative Mutation Analysis for MPNs (Myeloproliferative Neoplasms) Identification and quantitation of V617F mutation as a diagnostic indicator in polycythemia vera and other myeloproliferative neoplasms.

Provides molecular confirmation of morphologic, flow, and cytogenetic markers for an MPN allele. The determination of the percentage of the mutant amplicons present helps determine whether the patient is heterozygous or homozygous for the mutation.

Test results report the percentage of cells which have the mutant DNA present between 1% and 75%. Test results above 75% are reported as "POSITIVE, >75% mutant."

Sample JAK2 Graph

MPL W515L/K Mutation Detection (Thrombopoietin Receptor) for MPNs Identification of the W515L or W515K mutation as a diagnostic indicator for primary myelofibrosis (PMF) or essential thrombocythemia (ET). MPL testing is useful for patients with suspected MPN, including ET and PMF, particularly in those who are negative for the JAK2 V617F mutation. The test has a sensitivity down to 5% and can detect both the L and K mutations simultaneously.

T-Cell and B-Cell Clonality Assessment Identification of clonal T- and B-cell populations highly suggestive of T- and B-cell malignancies. Lineage determination of leukemias and lymphomas. Detects clonality that is highly sensitive (99% of B-cell malignancies and 94% of T-cell malignancies detected compared to Southern Blot Analysis). Useful for detecting residual disease or monitoring disease recurrence.

CEPBA Encodes a master regulatory transcription factor in hematopoiesis. CEBPA mutations are found in 10%–18% of CN-AML cases, and in about 40% of AML with 9q deletion occurring within a non-complex karyotype. CEBPA mutations are associated with higher CR rate and better RFS and OS.1

NPM1 NPM1 encodes a phosphoprotein with pleiotropic functions. NPM1 mutations are found in 25%–35% of all adult AML cases, in 45%–64% of CN-AML, in 35%–40% of AML with 9q deletion, and in about 15% of AML with trisomy 8. NPM1 mutations are associated with FLT3-ITD (~40%) and FLT3 TKD mutations. NPM1 is also associated with higher BM blast counts and serum LDH levels, myelomonocytic or monocytic morphology, and high CD33 and absent CD34 expression. NPM1 mutation is generally associated with better response to induction chemotherapy, and genotype “mutant NPM1 without FLT3-ITD” is associated with favorable relapse free survival and overall survival. Patients with “mutant NPM1 without FLT3-ITD” may not benefit from MRD transplantation in first complete response.1

FLT3 A member of the class III receptor tyrosine kinase family; FLT3 and its ligand play an important role in proliferation, survival and differentiation of hematopoietic progenitor cells. ITD FLT3-ITD are found in about 20% of all AML cases, and in 28%–34% of CN-AML. Association with inferior outcome; level of mutant allele likely of importance; homozygous FLT3 mutations as a result of mitotic recombination leading to partial uniparental disomy.1

Testing will be performed at Laboratory for Personalized Molecular Medicine (LabPMM) of San Diego, California.

cKIT Member of the class III receptor tyrosine kinase family; cKIT and its ligand stem cell factor have a key role in survival, proliferation, differentiation, and functional activation of hematopoietic progenitor cells. cKIT mutations are found in about 30% of core binding factor AML, and in rare cases of other AML types. cKIT mutations, in particular in exon 17, are associated with inferior outcome in many but not all studies.1

PML/RARA (Quantitative) Acute promyelocytic leukemia (APL) accounts for 5%–10% of acute myeloid leukemia and generally has a good prognosis with current treatment protocols. APL cells contain a fusion gene comprised of the downstream sequences of the retinoic acid receptor alpha gene (RARA) fused to the promoter region, and upstream sequences of one of several genes, the most common (>80%) being the promyelocytic leukemia gene (PML). The fusion gene is designated PML/RARA and may be seen in a karyotype as t(15;17)(q22;q12). Messenger RNA (PML/RARA) produced from the fusion gene can be detected using a polymerase chain reaction (PCR)–based assay, and indicates the presence of neoplastic cells. The PCR-based assay has greater sensitivity than standard methods such as morphology review, karyotyping, or fluorescence in situ hybridization (FISH). Recent studies have indicated that sensitive monitoring is important because the majority of patients who remain PCR-positive, or become PCR-positive again following treatment, will relapse and likely benefit from early intervention for residual/recurrent disease. This quantitative assay allows PML/RARA levels to be monitored rather than simply detecting the presence or absence of disease.2

K-RAS Mutation Analysis Identification of mutations in the K-RAS gene as an indicator of poor prognosis and likely poor response to EGFR inhibitors such as cetuximab, panitumumab, and erlotinib. K-RAS mutation analysis is helpful in the management of colorectal, lung, and other cancers.

B-RAF Mutation Analysis Identification of mutations in the B-RAF gene as an indicator of less-than-favorable prognosis and likely poor response to EGFR inhibitors such as cetuximab and panitumumab. B-RAF mutation analysis is helpful in the management of colorectal cancer.

DPD Pyrimidine analogues are widely used for chemotherapy of solid tumors, such as colorectal, breast, head/neck, ovarian, and pancreatic cancer. The majority (85%) of the administered dose of 5-fluorouricil (5-FU), and those of its derivatives, including capecitabine, undergoes degradation by the enzyme dihydropyrimidine dehydrogenase (DPD) before elimination. DPD catalyzes the initial rate-limiting step in the catabolism of 5-FU.

DPD enzyme levels affect the tumor response and toxicity associated with the drug as a result of the altered pharmacokinetics. Patients with low expression of DPD are more likely to respond to drug therapy at low doses, but experience the serious adverse side effects associated with 5-FU treatment at normal doses, including myelosuppression, cardiac toxicity, mucositis, hand-foot syndrome, and diarrhea.

MSI Approximately 15% of colorectal cancers demonstrate DNA duplication or contractions that are commonly found in short, tandemly repeated nucleotide sequences known as microsatellites. Loss of the DNA mis-match repair function is the most common cause, which is referred to as microsatellite instability.

Patients with stage II colorectal cancer whose tumors demonstrate high-frequency microsatellite instability (MSI-H) tend to have better overall survival compared to those whose tumor is classified as microsatellite stable (MSS). Adjuvant chemotherapy has not been shown to improve survival, though, in patients with MSI-H tumors; whereas, some improved survival benefit has been demonstrated when adjuvant chemotherapy is given to patients with MSS tumors.

MSI is also a useful screening test for Lynch syndrome, which is an inherited mutation in one of the mis-match repair (MMR) genes.

TS Thymidylate Synthase (TS) is the enzyme used to generate thymidine monophosphate (dTMP), which is subsequently phosphorylated to thymidine triphosphate for use in DNA synthesis and repair. The pyrimidines, 5-fluorouracil (5-FU), and capecitabine, achieve their therapeutic effect by the competitive inhibition of TS enzymatic activity. Intratumoral TS mRNA expression levels have been associated in an inverse fashion with survival in patients receiving treatment with 5-FU (i.e., low levels associated with favorable response).

ERCC1 Oxaliplatin is a third-generation platinum agent used in combination with 5-FU and leucovorin for colorectal cancer in both the adjuvant and metastatic settings. The cytotoxicity of oxaliplatin is believed to occur as a result of cross-link formation between complementary DNA strands. This ultimately results in DNA damage and apoptosis. Removal of these cross-links by the nucleotide excision repair (NER) pathway can result in resistance to oxaliplatin. The protein ERCC1 is one of the crucial components in the process of NER. Lower levels of ERCC1 result in a greater chance for oxaliplatin response because of decreased DNA repair.

EGFR Mutation Somatic mutations of the epidermal growth factor receptor (EGFR) are associated with response of advanced non-small cell lung cancer (NSCLC) to EGFR-specific tyrosine kinase inhibitors such as erlotinib and cetuximab. In a meta-analysis of seven Japanese studies that included 148 EGFR mutation-positive patients, the authors found that gefitinib confers a favorable progression-free survival (PFS; 10.7 months versus 6.0 months) and overall survival (OS; 27.7 months versus 25.7 months) in patients with EGFR mutations. Several additional studies have confirmed the favorable response to gefitinib rendered by the EGFR mutations.

About 80%-90% of NSCLC-associated mutations occur as deletions in exon 19, or as a single nucleotide substitution in exon 21, resulting in substitution of arginine for leucine at position 858 (L858R). Both of these mutations are associated with sensitivity to the small-molecule kinase inhibitors gefitinib or erlotinib. Other EGFR mutations are found in exon 18 (substitution of glycine at position 719 with alanine, serine, or cysteine), exon 20 (insertions and S768I), and exon 21 (L861Q).

EGFR Amplification EGFR amplification has been shown in certain cases of non-small cell lung cancer (NSCLC) to be a good predictor of response and longer survival in patients treated with gefitinib, erlotinib, or cetuximab. Tumors with high polysomy or gene amplification are associated with a better outcome, while disomy, trisomy, or low polysomy were associated with a lower level of response.

RRM1 Ribonucleoside-diphosphate reductase large subunit (RRM1) is an essential enzyme that catalyzes the conversion of deoxyribonucleotides from ribonucleotides, and is a target for the nucleoside analog gemcitabine. Gemcitabine, typically in combination with platinum-based therapeutics, is an important agent for treatment of non-small cell lung carcinoma (NSCLC). Several studies have linked high expression of RRM1 with a favorable prognostic outcome in newly resected NSCLC patients. Conversely, high expression of RRM1 has been demonstrated to be associated with poor response to gemcitabine-based therapeutics, either alone or in combination with cisplatin or carboplatin.

UGT1A1 UGT1A1 is responsible for the clearance of drugs (e.g., irinotecan) and normal metabolites such as bilirubin. Irinotecan toxicity (severe neutropenia) has been associated with the homozygous (*28/*28) genotype. A meta-analysis of 10 irinotecan pharmacogenetic studies enrolling a total of 825 patients assessed the correlation between irinotecan-induced hematologic toxicities in UGT1A1*28 patients, irinotecan dose, and overall toxicity.The results suggest the risk of experiencing irinotecan-induced hematologic toxicity for homozygous UGT1A1*28 patients is a function of the dose of irinotecan administered (see figures). The study supports the routine use of genotype analysis when dosing irinotecan at high doses (> 200 mg/m2), but suggests that testing was of modest benefit at intermediate doses.

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Circulating Tumor Cell (CTC) Test

CellSearch Circulating Tumor Cell (CTC) Test for Metastatic Breast, Colorectal, and Prostate Cancers Identification and enumeration of CTCs in metastatic breast, colorectal, and prostate cancer. Metastatic breast and prostate patients with <5 CTCs have significantly better survival than patients with >5 CTCs. The threshold for colorectal cancer is >3.

This test provides detection down to one CTC per 7.5ml of peripheral blood for monitoring effectiveness of treatment.

CTC Graph: Progression-Free Survival

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1. Döhner K; Döhner H. Molecular characterization of acute myeloid leukemia. Haematologica. 2008; 93(7); 976-983.
2. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/84114