Tests by Disease State

The focus at Genoptix is to provide comprehensive and quality diagnostic services for all disease states in the realm of hematomalignancies (cancers of the blood). We understand that accurate diagnosis, treatment, and monitoring are keys to effective patient management. Our deep level of expertise in this specialty of cancer allows us to provide physicians and their patients with information that paints a complete clinical picture for physicians to best manage their patients.


Tests for Leukemia

Morphology
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 immunhistochemistry (up to 30 stains and/or antibodies) and special stains such as iron and reticulin stains.

Flow Cytometry Tests
Intelligent Flow ProfileFlow cytometric phenotyping for hematologic malignancies. Utilizes 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 minimal residual disease (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 GPI linkage and determination of reduction or loss of specific antigens on monocytes, granulocytes, and lymphocytes. Immunophenotyping specifically for suspected PNH.

Cytogenetics/FISH
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.

CML: Philadelphia chromosome t(9;22) Male Karyotype with Complex Abornmalities

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.

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.

Molecular Tests

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 prognosis 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 CML. Offers exceptional sensitivity (1:10,000 cells) for serial monitoring of residual disease and molecular response to treatment.

T-Cell and B-Cell Identification of clonal T- and B-cell populations highly suggestive of T- and B-cell malignancies. Lineage determination of leukemias and lymphomas. Detects clonatity 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.

CEBPA 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 associated with higher CR rate and better RFS and OS.1

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 associated with FLT3-ITD (~40%) and FLT3 TKD mutations. Association with females, higher BM blast counts and serum LDH levels, myelomonocytic or monocytic morphology, and high CD33 and absent CD34 expression. NPM1 mutation in general associated with better response to induction chemotherapy; genotype “mutant NPM1 without FLT3-ITD” associated with favorable RFS and OS; patients with “mutant NPM1 without FLT3-ITD” may not benefit from MRD transplantation in first CR.1

FLT3 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; KIT and its ligand stem cell factor have a key role in survival, proliferation, differentiation, and functional activation of hematopoietic progenitor cells. KIT mutations found in about 30% of core binding factor AML, and in rare cases of other AML types. KIT mutations, in particular in exon 17, associated with inferior outcome in many but not all studies.1

PML-RARA (Quantitative) Acute promyelocytic leukemia (APL) accounts for 5% to 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

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Lymphoma

Morphology
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 immunhistochemistry (up to 30 stains and/or antibodies) and special stains such as iron and reticulin stains.

Flow Cytometry Tests


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

Cytogenetic/FISH
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.

Normal female karyotype Abnormal female karyotype showing deletion of 7q

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.

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.

Molecular Tests
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.

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Myeloma

Morphology
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 immunhistochemistry (up to 30 stains and/or antibodies) and special stains such as iron and reticulin stains.

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

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.

Cytogenetics/FISH
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.

Normal male karyotype Abnormal male karyotype with loss of Y

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.

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.

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Myelodysplastic Sydrome (MDS)

Morphology
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 immunhistochemistry (up to 30 stains and/or antibodies) and special stains such as iron and reticulin stains.

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

Cytogenetics/FISH
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.

Normal female karyotype Karyotype shows Trisomy 8

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.

Fluor escence 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.

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Myeloproliferative Disorders/Neoplasms (MPD/MPN)

Morphology
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 immunhistochemistry (up to 30 stains and/or antibodies) and special stains such as iron and reticulin stains.

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

Cytogenetics
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.

Normal female karyotype Abnormal karyotype reveals Monosomy 7

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.

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.

Molecular Tests
bcr/abl t(9;22) Quantitative GenoTRACE® Assay for CML (Chronic Mylogenous Leukemia) Real-Time PCR for detection of t(9;22) and quantitation in CML. Offers exceptional sensitivity (1:10,000 cells) for serial monitoring of residual disease and molecular response to treatment and other therapeutics.

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 a 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.

MPL W515L/K Mutation Detection (Thrombopoietin Receptor) for MPNs (Myeloproliferative Neoplasms) 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 MPD, including ET, 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.

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Metastatic Breast, Colorectal, and Prostate Cancers

Circulating Tumor Cell (CTC) Test CellSearch™ for Metastatic Breast, Colorectal, and Prostate CancersIdentification 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.

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

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Non-Small Cell Lung Cancer

CARBOPLATIN AND CISPLATIN1-4

ERCC1 predicts the likelihood of response to platinum-based therapy

  • High levels of ERCC1 are associated with relative resistance, while low levels are associated with relative sensitivity.
  • In the absence of therapy, high levels are suggestive of better overall survival probability for patients with NSCLC.

CETUXIMAB AND ERLOTINIB5-8

EGFR mutation and EGFR amplification help predict the likelihood of response to EGFR inhibitors

  • EGFR amplification in tumors, high polysomy or gene copy number, is associated with better treatment response to EGFR inhibitors.
  • Mutations in the EGFR gene are a positive predictor of effectiveness of tyrosine kinase inhibitors (TKIs) such as erlotinib.
  • Mutations in the EGFR are prognostic with or without chemotherapy.

GEMCITABINE4,9,10

Ribonucleotide reductase M1 (RRM1) predicts the likelihood of response to gemcitabine-based therapy

  • High expression of RRM1 in tumor tissue is predictive of poor response to gemcitabine treatment.
  • In the absence of therapy, high levels are suggestive of better overall survival probability for patients with NSCLC.

IRINOTECAN11,12

UGT1A1 is involved in irinotecan metabolism and toxicity tolerance

  • UGT1A1 gene mutation is associated with decreased ability to metabolize irinotecan, resulting in potential for severe toxicity.

PEMETREXED13,14

Thymidylate synthase (TS) gene expression predicts likelihood of response to pemetrexed

  • Low levels of TS gene expression may be associated with better treatment response in NSCLC.

  1. Olaussen K, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355:983-991.
  2. Cobo M. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small cell lung cancer. J Clin Oncol. 2007;25(19):2747-2754.
  3. Lord RV, Brabender J, Gandara D, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002;8(7):2286-2291.
  4. Ceppi P, Volante M, Novello S, et al. ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small cell lung cancer treated with cisplatin and gemcitabine. Ann Oncol. 2006;17(12):1818-1825.
  5. Slebos RJ, Kibbelaar RE, Dalesio O, et al. K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Eng J Med. 1990;323(9):561-565.
  6. Zhu CQ, da Cunha Santos G, Ding K, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol. 2008;26(26):4268-4275.
  7. Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer—molecular and clinical predictors of outcome. N Eng J Med. 2005;353(2):133-144.
  8. Eberhard DA, Johnson BE, Amler LC, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005;(23)25:5900-5909.
  9. Bepler G, Kusmartseva I, Sharma S, et al. RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small cell lung cancer. J Clin Oncol. 2006;24(29):4731-4737.
  10. Rosell R, Danenberg KD, Alberola V, et al. Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin Cancer Res. 2004;10(4):1318-1325.
  11. Hoskins JM, Goldberg RM, Qu P, et al. UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst. 2007;99(17):1290-1295.
  12. Rouits E, Charasson V, Petain A, et al. Pharmacokinetic and pharmagenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer. Br J Cancer. 2008;99(8):1239-1245.
  13. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naïve patients with advanced-stage non-small cell lung cancer. J Clin Oncol. 2008;26(21):3543-3551.
  14. Ceppi P, Volante M, Saviozzi S, et al: Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer. 2006;107(7):1589-1596.


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Colon Cancer

5-FU AND CAPECITABINE1-3

TS, MSI, and DPD indicate likelihood of 5-FU-based treatment effectiveness and toxicity

  • Low levels of TS expression in tumors are associated with better patient response to 5-FU and capecitabine1-3
  • Patients with DPD deficiency cannot metabolize 5-FU as effectively, which predicts a higher chance of toxicity4-7
  • Stage II CRC patients with MSI HIGH status tend to not benefit from 5-FU adjuvant therapy8-10

FOLFOX VS. FOLFIRI

ERCC1 and UGT1A1 help in the decision between FOLFOX and FOLFIRI treatment to increase potential effectiveness and decrease toxicity

  • High levels of ERCC1 are associated with oxaliplatin resistance1
  • A positive UGT1A1 mutation is associated with a decreased ability to metabolize irinotecan in FOLFIRI, resulting in an increased likelihood of severe toxicity11
  • Mutations in the EGFR are prognostic with or without chemotherapy.

EGFR INHIBITORS (cetuximab and panitumumab)

K-RAS indicates likelihood of metastatic tumor response to EGFR inhibitors

  • Positive K-RAS results are predictive that a patient's metastatic tumor will not respond to EGFR inhibitors12-14
  • Positive B-RAF mutation is an unfavorable prognostic indicator for patients regardless of treatment

SERIAL MONITORING

Our CTC test results:

  • Provide helpful insights into metastatic CRC status and prognosis15
  • Are a valuable adjunct to imaging and provide similar predictive and prognostic information to imaging, but earlier15
  • Can be followed over time

And, we keep your patients' test results on file so that every time you reorder their CTC, we send you a report charting their progress over time.


  1. Shirota Y, et al. ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol. 2001;19(23):4298-304.
  2. U chida K, et al. Thymidylate synthase, dihydropyrimidine dehydrogenase, ERCC1, and thymidine phosphorylase gene expression in primary and metastatic gastrointestinal adenocarcinoma tissue in patients treated on a phase I trial of oxaliplatin and capecitabine. BMC Cancer. 2008;8:386.
  3. Soong R, et al. Prognostic significance of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase protein expression in colorectal cancer patients treated with or without 5-fluorouracil-based chemotherapy. Ann Oncol. 2008;19(5):915-8.
  4. Meta-Analysis Group In Cancer. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol.1998;16(11):3537-41.
  5. van Kuilenburg AB, et al. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum Genet. 1999;104(1):1-9.
  6. van Kuilenburg AB, et al. Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase (DPD) deficiency after administration of 5-fluorouracil: frequency of the common IVS14+1G>A mutation causing DPD deficiency. Clin Cancer Res. 2001;7(5):1149-53.
  7. Morel A, et al. Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol Cancer Ther.2006;5(11):2895-904.
  8. Sargent DJ, et al. Confirmation of deficient mismatch repair (dMMR) as a predictive marker for lack of benefit from 5-FU based chemotherapy in stage II and III colon cancer (CC):a pooled molecular reanalysis of randomized chemotherapy trials. J Clin Oncol. 2008;26(15 Suppl):4008.
  9. Popat S, et al. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23(3):609-18.
  10. Des Guetz G, et al. Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis. Eur J Cancer.2009;45(10):1890-6.
  11. Rouits E, et al. Pharmacokinetic and pharmagenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer. Br J Cancer. 2008;99(8):1239-45.
  12. Lièvre, A, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26(3):374-9.
  13. Amado RG, et al. Wild-type (WT) KRAS is required for panitumumab efficacy in patient-with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626-34.
  14. Di Nicolantonio F, et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008;26(35):5705-12.
  15. Cohen SJ, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol.2008;26(19):3213-21.

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