Chromosomal rearrangements

Sometimes these aberrations are the sole observed anomaly in the karyotypes, and sometimes they involve balanced changes, mostly reciprocal translocations. In these instances it is reasonable to assume that they represent pathogenetically important changes that may involve the generation of new cancer-specific fusion genes.

Some of the possible Chromosome Structural changes that may occur.

In the project “Gene consequences of cancer-specific chromosomal rearrangements” we propose to examine in molecular detail a series of such novel changes so as to find out which are their gene-level consequences. We shall mostly use various fluorescence in situ hybridization-based techniques, both to determine the precise breakpoint positions and as array-based comparative genomic hybridization, combined with more exclusively molecular genetic methods such as RACE PCR and sequencing. Microdissection of the rearranged chromosomes with subsequent amplification prior to molecular analysis is a central methodology. The information obtained will provide insight into the mechanism of tumorigenesis in the tumors and tumor types examined, and may also sharpen our diagnostic abilities as well as our understanding of what distinguishes malignant from benign neoplastic growth.

Planned examinations of new cancer-specific chromosomal abnormalities

• Precise identification of the additional material of unknown origin sitting on the short arm of chromosome 18 in chronic lymphatic leukaemia
• Precise identification of chromosomal breakpoints and gene involvement in the translocation t(2;19)(q11;q13) occurring as the as the sole cytogenetic abnormality in marginal lymphoma
• Precise identification of chromosomal breakpoint and gene involvement in the three-way translocation t(2;3;19)(q33;p13;p13) occurring as the sole cytogenetic abnormality in benign chondroma
• Precise identification of chromosomal breakpoint and gene involvement in the translocation t(2;17)(q23;q23) occurring as the sole cytogenetic abnormality in low grade fibromyxosarcoma
• Precise identification of chromosomal breakpoint and gene involvement in the translocation t(12;13)(q21;q22) occurring as the sole cytogenetic abnormality in acute myeloid leukaemia
• Precise identification of chromosomal breakpoint and gene involvement in the translocation t(4;6)(q13;q21) occurring as the sole cytogenetic abnormality in spindle cell sarcoma