DNA-FISH Probes

Fluorescent in situ hybridization (FISH) is a sensitive and accurate technique that allows the detection of chromosome aberrations. In this method, a single-stranded fluorescent-labeled nucleic acid sequence (probe) complementary to a target genomic sequence is hybridized to metaphase chromosomes and interphase nuclei to detect the presence and absence of a given abnormality. FISH complements traditional cytogenetic karyotype analysis. The chief advantage of FISH is that is can be applied to non-dividing cells and a variety of specimen types. FISH is a method of choice for diagnosis, prognosis, treatment response, and minimal residual disease detection in hematopoietic neoplasms (leukemia, lymphomas, multiple myeloma, and myelodysplasia) and solid tumors (breast cancer, non-small cell lung cancer, colorectal cancer, and cervical cancer).

CGI is developing innovative DNA-FISH probe panels dedicated to help clinicians in prognosis, risk stratification, and clinical management of renal cancers and in the detection of HPV-associated precancer and cancers. The development and validation of these new FISH-based assays is expected to place CGI as the leader of cancer molecular diagnostics.

FISH-based Renal Cancer Detection (FReCaD™) assay

In most cancers, diagnosis predominantly relies upon pathologic classification of a specimen and/or biopsy. With the well-documented increased use of image-guided fine needle biopsy for diagnostic purposes, the material obtained can often be of inadequate quantity and quality for morphologic examination. For renal cancer, where both malignant and benign lesions are frequent, there is a need to develop cancer detection tests to assist in classification as benign versus malignant that is not based on cell morphology alone. The FISH-based Renal Cancer Detection (FReCaD™) assay is one such assay designed by CGI to distinguish the four predominant renal cortical neoplasm subtypes (three malignant and one benign) based on inherent differential genetics without the use of invasive methods. This test involves a series of fluorescent in-situ hybridizations in a biopsy sample using a probe panel associated with each of the subtypes. This unique and innovative panel of probes and hybridization strategy has been approved for intellectual property protection (US Pat. Application # 11/932,422). The impact of diagnostic assistance of the FReCaD™ assay is not only limited to small lesions to distinguish benign versus malignant to avoid surgery, but also applicable to larger neoplasms to risk-stratify patients of local or regionally advanced disease, and to metastatic disease where drug trials are currently based on post-surgical tumor diagnosis causing delays to potentially curative treatment. At CGI, the FreCaD™ assay is currently undergoing a large clinical validation of kidney biopsies with another to be initiated for fine needle aspirates of renal masses.

FISH-based HPV-associated Cancer Test (FHACT^TM)

The success of screening programs for the detection of precancer lesions of cervical cancer based on the appearance of abnormal cells in cytology specimens is well known, but there is a great need to identify additional biomarkers to increase the sensitivity with which precancer and cancer are detected. Given the well accepted etiologic involvement of high-risk human papillomavirus (HPV) in this disease, diagnostic assays implemented for the detection of high risk HPV types has improved the sensitivity. Genomic abnormalities observed in HPV-associated cancers can also serve as biomarkers of cancer progression, whose detection in a FISH based assay can be implemented with precancer and cancer screening programs to enhance sensitivity. The FISH-based HPV-associated Cancer Test (FHACT™) developed at CGI is a single hybridization assay for the detection of chromosomal regions often observed early in HPV-associated precancers, and as such represent biomarkers of HPV-associated cancer progression. The FHACT™ is currently undergoing clinical validation in large panels (1000 each) of cervical and anal cytology specimens, and is anticipated to have extensive utilization in screening programs not only for cervical and anal cancers but also for other HPV-associated cancers such as oral and oropharyngeal cancers.