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The Tissue Core of this consortium provides the necessary infrastructure for all the projects to achieve their potential and expedite their findings.

Cytogenetics (FISH)

Tissue Core | Cytogenetics (FISH) | Cellular Kinetics and VH studies

Cytogenetic abnormalities in B-cell CLL are important prognostic indicators for predicting disease progression and treatment response. Interphase FISH (Fluorescence In Situ Hybridization) is widely used in clinical practice to study patients with CLL. This technology is useful to detect specific gene anomalies and various aneuploid conditions in neoplastic cells. FISH can be performed on blood and bone marrow aspirates or smears, paraffin embedded tissues, touch preparations, and many other tissue preparations. Interphase FISH can be used to establish the percentage of neoplastic and normal cells in both interphase and metaphase cells before and after therapy, and therefore can be used to assess therapy and monitor remission. Some FISH tests can detect levels of disease that are less than 1% and are therefore particularly useful to study minimal residual disease, though most FISH assays for CLL have a normal cutoff of approximately 7%.

The most common cytogenetic anomalies in CLL involve chromosomes 6, 11, 12, 13, 14 and 17.

Chromosomal anomalies detected by interphase FISH are among the most important factors predicting survival in B-CLL(21). FISH-detected chromosome anomalies have also been associated with different clinical outcomes and may be associated with IGHv mutation status, CD38 expression, ZAP 70, antigen expression on leukemic B-lymphocytes, cell morphology and other biological features(2,3,27,29). Today many investigators use the following hierarchical risk model of FISH anomalies in B-CLL defined by Dohner et al. (27) and Dewald et al (21) with 17p- as the most aggressive and 13q-x1 as the least aggressive: 17p- ® 11q- ® 6q- ® +12 ® normal ® 13q-x2 ® 13q-x1.

The Tissue Core has standardized interphase FISH among the CRC cytogenetics sites (uniform scoring and data-entry). This validation has provided accurate interphase FISH studies for CRC clinical trials and CRC research investigators across the United States. In addition the CRC FISH information associated with each CRC CLL patient has used for genetic studies by Project 1 of this consortium.

Cytogenetics Lab Directors
Click here to download the Cytogenetics (FISH) contact list


Daniel Van Dyke, Ph.D.
Mayo Clinic

Nyla Heerema, Ph.D.
Ohio State University Cancer Center

Paola Dal Cin, Ph.D.
Dana-Farber Cancer Institute

Ayala Aviram, Ph.D.
North Shore-Long Island Jewish Health System

Marie dell'Aquila, Ph.D.
Moores UCSD Cancer Center


CRC Cytogenetics/FISH Team

References

Genomic Aberrations and Survival in Chronic Lymphocytic Leukemia. Hartmut Döhner, M.D., Stephan Stilgenbauer, M.D., Axel Benner, M.Sc., Elke Leupolt, M.D., Alexander Kröber, M.D., Lars Bullinger, M.D., Konstanze Döhner, M.D., Martin Bentz, M.D., and Peter Lichter, Ph.D. The New England Journal of Medicine, December 28, 2000. Volume 343 Number 26.

Additional Genetic High-Risk Features Such As 11q Deletion, 17p Deletion, and V3-21 Usage Characterize Discordance of ZAP-70 and VH Mutation Status in Chronic Lymphocytic Leukemia. Alexander Kröber, Johannes Bloehdorn, Sebastian Hafner, Andreas Bu¨hler, Till Seiler, Dirk Kienle, Dirk Winkler, Markus Bangerter, Richard F. Schlenk, Axel Benner, Peter Lichter, Hartmut Döhner, and Stephan Stilgenbaue. Journal of Clinical Oncology. Volume 24, Number 6, February 20, 2006.

Dewald, G. W., S. R. Brockman, et al. (2003). "Chromosome anomalies detected by interphase fluorescence in situ hybridization: correlation with significant biological features of B-cell chronic lymphocytic leukaemia." Br J Haematol 121(2): 287-95.

Byrd, J. C., L. Smith, et al. (2003). "Interphase cytogenetic abnormalities in Chronic Lymphocytic Leukemia may predict response to rituximab." Cancer Res 63(1): 36-8.


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