Microscopy Genomics QM-FISH
Single cell genomics by QM-FISH in determining risk for metastasis at the initial stage of diagnostics. Critical for treatment decisions.
The immediate goal (3a) is to identify specific genes/chromosomal regions that show copy number abnormalities (CNAs) high-risk, in early metastasizing tumors. The long term goal (3b) is to finish the development of the unique platform for Microscopy Image Genomics to be used for multi-centric validation studies and later introduced as a powerful, treatment guiding PCM tool in clinical pathology 3a. The new techniques developed in Mike Wigler´s laboratory (CSHL) for sequencing morphologically identified, small tumor regions (representing sub-clones containing 1000 – 5000 cells) dissected from formalin fixed, paraffin embedded (FFPE) tumor material works extraordinary well and provides information about CNAs with high degree of resolution.
A clear picture is emerging. Low-risk CNAs, probably representing tumor growth, are seen in almost all tumors, while a limited number of high-risk CNAs (30 to 50) are only seen in early metastasizing tumors. Very recent studies performed during the past 6 months show that such high-risk CNAs can be seen in very small tumors (4 to 8 mm) that early develop distant metastases.
3b. Major, break-through improvements during the past 12 months of the molecular hybridization technology resulted in a 10-fold increase in signal to noise ratio as compared to our original QM-FISH technique, which in itself showed a 3-5 times higher signal to noise ratio as compared to standard FISH. This opened the possibility to use low-power magnification (20X) instead of high-power magnification (63X) in the microscope, which increases the measurement capacity with a factor of 50. This will be particularly important when addressing the critical problem of tumor heterogeneity by scanning CNAs in large microscopic fields. Furthermore, the increased measurement capacity will now allow more comprehensive, large-scale validation studies.