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Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system Junior

Abstract

The breast cancer resistance protein, also known as ABCG2, is one of the most highly studied ATP-binding cassette (ABC) transporters because of its ability to confer multidrug resistance1,2. The lack of information on the physiological role of ABCG2 in humans severely limits cancer chemotherapeutic approaches targeting this transporter. We report here that ABCG2 comprises the molecular basis of a new blood group system (Junior, Jr) and that individuals of the Jr(a−) blood type have inherited two null alleles of ABCG2. We identified five frameshift and three nonsense mutations in ABCG2. We also show that the prevalence of the Jr(a−) blood type in the Japanese and European Gypsy populations is related to the p.Gln126* and p.Arg236* protein alterations, respectively. The identification of ABCG2−/− (Jr(a−)) individuals who appear phenotypically normal is an essential step toward targeting ABCG2 in cancer and also in understanding the physiological and pharmacological roles of this promiscuous transporter in humans.

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Figure 1: The ABCG2 transporter encodes the Jra blood group antigen.
Figure 2: Null alleles of ABCG2 are responsible for the Jr(a−) blood type.

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Acknowledgements

The authors are indebted to all present and past members of the CNRGS for identifying and conserving Jr(a−) blood samples and extracting genomic DNA. We greatly appreciate M. Le Gall for her thoughtful comments on the manuscript. This study was supported in part by the INTS, Inserm and Paris Diderot University (Paris 7). B.A.B. was funded by the Vermont Genetics Network through a grant from the US National Institutes of Health/National Center for Research Resources (P20 RR16462).

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Correspondence to Lionel Arnaud.

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Saison, C., Helias, V., Ballif, B. et al. Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system Junior. Nat Genet 44, 174–177 (2012). https://doi.org/10.1038/ng.1070

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