MICRODISSECTION BASED CLONING OF A TRANSLOCATION BREAKPOINT IN A HUMAN-MALIGNANT MELANOMA

Chromosome translocations in human malignancies have identified the ge nomic location of several important growth-regulatory sequences (e.g., cellular oncogenes and suppressor genes). Melanomas are characterized by recurring chromosome alterations, including deletion or translocat ions of the long arm of chromosome 6 (6q). This report details our eff orts to clone the t(1;6)(q21;q14) breakpoint in a malignant melanoma t o further our understanding of the biology of these tumors. The strate gy utilized combined microdissection of the translocation chromosome, development and characterization of a DNA microclone library, isolatio n of cosmids and YACs from the breakpoint region, ordering of clones b y two-color metaphase/interphase fluorescence in situ hybridization, a nd finally, identification of a YAC spanning the translocation breakpo int. By analogy to other tumor systems, molecular examination of the c hromosome 6 breakpoint may provide insight into the pathobiology of th is important neoplasm.