Bloom syndrome : an example of how an genomic instability leads to cancer

Abstract

Bloom Syndrome (BS) is an autosomal recessive disorder whose phenotype consists of short height, a facial erythematous rash, UV sensitivity, microcephaly, and a narrow face. Cases have been documented all over t he world but seem to be prevalent in individuals of Ashkenazic Jewish descent. The underlying cause of this condition is a mutation in the BLM gene on chromosome 15, which codes for the helicase enzyme, BLM. This protein is involved in DNA repair and acts with p53 to initiate apoptosis. Molecular analyses reveal several chromosomal breaks and sister chromatid exchanges that are around 10 times more frequent than in normal cells. These observations are thought to be a result of an alternative pathway which tries to resolve stalled replication forks during the process of DNA replication, hence sparing the cells from apoptosis. This primitive evolutionary survival mechanism allows some BS cells to survive, but at the price of an increased incidence of malignancies.