Array Comparative Genomic HybridizationMicroarray-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 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 (MatBA®) 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 MatBA®-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 MatBA® is particularly well suited for the detection of these abnormalities in these lymphoma types considering the ability to perform MatBA® on DNA extracted from FFPE specimens. The MatBA®-DLBCL Array-CGH and MatBA®-MCL Array-CGH tests have been both CLIA and New York State approved for clinical use.
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. MatBA® has the potential to be incorporated as a diagnostic test to detect gain/loss associated with inferior disease course and transformation to aggressive DLBCL. The MatBA®-FL Array-CGH test has also been both CLIA and New York State approved for clinical use.