CGH-Microarray
Microarray-based technology has provided a platform on which a large number of genomic aberrations can be assessed in a single experiment. CGI is focused on one application of the microarray technology, known as array comparative genomic hybridization or array-CGH, to detect DNA copy number changes (gain/loss) frequently observed in cancers.
Targeted arrays in various stages of design and development include those for diagnostic and prognostic purposes in lymphomas, genitourinary cancers, gynecological cancers and leukemias.
Mature B-cell neoplasm array: MatBA™
Mature B-cell neoplasms arise in B-cells that have entered germinal centers within lymph nodes as part of the immune response. They display great heterogeneity at the clinical, pathologic, and genetic levels and represent 6-7% and 5-6% of all new estimated cancer cases and deaths respectively in the US in 2009. They are the fifth most common neoplasm in both males and females, and of the 103,960 estimated new cases in 2009, 20,860 comprise diffuse large B-cell lymphoma (DLBCL), 20,580 multiple myeloma (MM), 15,490 chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), 14,900 follicular lymphoma (FL), 8,510 Hodgkin’s lymphoma (HL), 6,000 marginal zone lymphomas (MZL) (including the three subtypes: extranodal marginal zone of mucosa-associated lymphoid tissue [MALT], nodal marginal zone, and splenic marginal zone), and 3,730 mantle cell lymphomas (MCL), as the major subtypes. With the exclusion of HL, 32,520 deaths are expected in 2009 in the US as a result of these neoplasms.
Diagnosis of these neoplasms relies mostly on the pathologic examination of biopsy material, be it either of an incisional or excisional biopsy of a suspect lymph node, a fine needle aspirate of a suspect lymph node (as yet to be considered adequate for initial diagnosis, unless it is the only safe option), or a bone marrow aspirate. Unlike other cancers, rarely are other biopsy/surgical procedures performed prior to the initiation of treatment, thus limiting the amount of tissue available for diagnostic and prognostic purposes. CGI has optimized the utility of array-CGH so that it can be routinely applied to the study of a range of specimen types including formalin-fixed paraffin-embedded (FFPE) specimens, often the only specimen available for analysis.
CGI has designed an oligonucleotide-based array (MatBATM) for the detection of gains and losses in mature B-cell neoplasms for utilization within a clinical laboratory. For CLL/SLL, it’s primary value is in routine prognostication, and as an assay, has been approved in the CGI Diagnostic Laboratory by both CLIA and New York State. In this disease where approximately 50% patients have an aggressive course and 50% can live for many years without requiring treatment, robust prognostication is highly desirable. Together with IGHV mutation status, the MatBATM-CLL array-CGH test provides important genetic-based information to guide clinical management of this disease. For the aggressive lymphomas, DLBCL and MCL, overall survival and progression-free survival following front-line therapy are important parameters for which clinicians need robust biomarkers. Genomic gain and loss have been reported to be associated with these clinical features and the use of MatBATM is particularly well suited for the detection of these abnormalities in these lymphoma types considering the ability to perform MatBATM on DNA extracted from FFPE specimens. FL is an indolent lymphoma where clinical management can range from a wait and watch approach to immunochemotherapy, where currently clinical and pathologic features are used to assist decision-making. MatBATM has the potential to be incorporated as a diagnostic test to detect gain/loss associated with inferior disease course and transformation to aggressive DLBCL.
Pipeline of MatBA™ products line
Genitourinary cancer array: UroGenRA™, UGenRA™
Cancers of the genitourinary system (prostate, testis, penis, cervical, uterine, ovarian, vulva, kidney, bladder, and ureter cancers) account for close to 30% of all estimated new cancer cases in the USA with the three most prevalent being prostate, bladder, and kidney cancers. The estimated deaths caused by these in 2010 are expected to be 32,050, 14,680, and 13,040 respectively, comprising ~10% of all cancer-related deaths. Thus, although generally characterized by early stage detections and encouraging five-year survival rates, these cancers still represent major health risk and substantial medical cost burden to the public with their high rates of incidence. In women, the three most frequent genital system cancers are endometrial, ovarian, and then cervical with a total overall expected deaths in 2010 to be 26,000 with ovarian cancer accounting for over half. Developing sophisticated, state-of-the-art molecular assays that enable more accurate diagnosis and/or prognosis of these cancers will not only benefit the patients by offering more appropriate treatments but also effectively reduce the unnecessary medical cost associated with surgery, long-term follow-up surveillance, or adjuvant therapy after the treatment.
UroGenRA™
UroGenRATM is a CGI custom-designed oligonucleotide array for implementation within a clinical laboratory as an array-CGH-based diagnostic/prognostic tool for kidney, prostate, and bladder cancers. It was designed to detect gains and losses that frequently occur in these three cancer types and that have the potential to differentially diagnose and/or stratify patients to assist and guide clinical management. For kidney cancer, it is specifically designed to classify tumors into the four main types (three malignant, one benign) critical at several levels in patient management: diagnosis of image-guided needle biopsies of small incidentally discovered kidney masses providing rationale for surgical/non-surgical management, diagnosis in patients with larger neoplasms to stratify for risks of local or regionally advanced disease that can be factored in to treatment selection recommendations (i.e., extent of surgical intervention, less invasive options or ablation), in those with metastatic disease, where drug trials are currently based on post-surgical tumor diagnosis, and potentially in the diagnosis of the so-called morphologically “unclassified” renal cancers. Additionally within the predominant subtype, clear cell renal cell carcinoma, prognostication is feasible based on the presence/absence of gain and loss of certain genomic regions. For prostate cancer, UroGenRATM, has the potential to assess prostate core/needle biopsy genomic variability, to identify biomarker for inclusion in nomograms for assessment of risk of biochemical recurrence, to assess radiocurability and treatment options for intermediate risk patients, and to explore the genomic aberrations of circulating tumor cells. Forbladder cancer, UroGenRATM has application in identifying tumors most likely to recur, and of muscle-invasive lesions those most likely to benefit from treatment.
Pipeline of UroGenRA™ Product Line
UGenRA™
UGenRATM is a CGI custom-designed oligonucleotide array designed to detect gains and losses of genomic material in endometrial, ovarian, and cervical cancers. Endometrial hyperplasia is a precursor lesion of endometriod endometrial carcinoma (EEC) and since about 50% of women with atypical hyperplasia also have concurrent EEC, it is important to identify those precursor lesions more likely to progress to and those with frank cancer. UGenRATM offers the opportunity to identify such specimens and potentially guide clinical management. Another potential application is to stratify those tumors likely to recur, permitting the identification of patients most likely to benefit from adjuvant therapy. Risk-stratification of stage III/IV ovarian cancer patients after cytoreductive surgery for front-line platinum taxane-based chemotherapy is a potential application for UGenRATM, and the design currently contains the sites of genomic gain/loss with such prognostic value. For any of the three cancers, genomic gain/loss associated with response to particular therapies can be assessed using UGenRATM, especially with the need of only small amounts of starting material and the ability to perform UGenRATM on FFPE specimens.
Pipeline of the UGenRATM Product line
Leukemia array: LeukA™
Leukemia is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation of blood cells,usually white blood cells. Leukemia is the 9th most common type of cancer diagnosed in the US in 2009. There are many leukemia subtypes with clinical course ranging from indolent to aggressive. Although a number of drugs exist for treating leukemia, it is known that the effectiveness of these drugs depends more on the underlying genetics of cancer cells than on the histological classification of leukemia subtypes.
CGI is in the preliminary phase of designing a CGH-microarray that detects gains and losses in DNA associated with differential diagnosis and prognosis of the main types and subtypes of leukemia: LeukA™.
Pipeline for LeukA™
