Crossovers and Cancer

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Science  21 Dec 2012:
Vol. 338, Issue 6114, pp. 1513
DOI: 10.1126/science.338.6114.1513-b

Many cancer-related genes involve variants of genes involved in DNA repair, which often also play a role in chromosomal recombination. Hussin et al. used exome sequencing to analyze a family with two siblings that have childhood B cell precursor acute lymphoblastic leukemia (B-ALL). They found that the mother carried a rare variant of PRDM9, a protein that regulates recombination hotspot usage in humans. Examination of the recombination profiles between the parents and offspring revealed an unusual maternal recombination profile in the two B-ALL–affected siblings. The authors then sequenced the exomes of a cohort of 44 parents whose children are affected by B-ALL and identified an excess of rare alleles relative to control populations. These findings were confirmed in an independent cohort of B-ALL–affected children and infants. Analysis of the motifs bound by the PRDM9 variants revealed that they were more likely to be found in segmental duplications within the genome in genes associated with ALL. On the basis of their investigations, the authors propose that PRDM9-mediated effects on meiotic recombination may contribute to the development of childhood leukemogenesis.

Genome Res. 10.1101/gr.144188.112 (2012).

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