Haploinsufficiency Comes into Bloom

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Science  20 Sep 2002:
Vol. 297, Issue 5589, pp. 1953
DOI: 10.1126/science.297.5589.1953k

A widely accepted model of cancer genetics proposes that tumorigenesis requires inactivation of both alleles of a tumor suppressor gene. However, recent evidence from mouse models suggests that mutation of only one allele (producing “haploinsufficiency,” a state in which the wild-type tumor suppressor is present at half its normal dose) may also affect cancer risk. Goss et al. (p. 2051) now report that mice show an enhanced susceptibility to tumor formation when they carry one mutant and one wild-type copy of Blm, the causative gene for the human cancer predisposition disorder Bloom syndrome. In a companion study of a human population, Gruber et al. (p. 2013) find that Ashkenazi Jews heterozygous for the same BLM mutant allele are more than twice as likely to develop colorectal cancer as control subjects.

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