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Chromosome breakage syndromes and cancer.

There exist numerous genetic disorders, marked by chromosome instability, that are strikingly associated with various cancers. Both the chromosomal instabilities and neoplastic outcomes are related to abnormalities of DNA metabolism, DNA repair, cell-cycle governance, or control of apoptosis. Among these diseases are ataxia telangectasia and Nijmegen breakage syndrome, with increased incidences of lymphomas. Bloom syndrome, Werner syndrome, and Rothmund-Thompson syndrome, each characterized by a DNA helicase defect, are associated with early incidences of different cancers. Other diseases combining the phenotype of chromosomal instabilities and neoplastic development are Fanconi anemia and breast cancers associated with mutant BRCA1 and BRCA2 genes. The cloning of the encoding genes and the characterization of their products have resulted in partial understanding of the pathways of cellular DNA surveillance and maintenance of genomic rectitude. The exact pathways fully linking the genetic defect mechanisms to the eventual development of various neoplasias remain to be elucidated, but progress in defining the molecular genetics of these entities suggests that many of them are disorders of DNA recombination. Each defect involves a separate protein in these complex pathways.