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

Nat Genet. 2012 Jan 15;44(2):174-7. doi: 10.1038/ng.1070.

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 resistance. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics*
  • Asian Continental Ancestry Group / genetics
  • Asian Continental Ancestry Group / statistics & numerical data
  • Blood Group Antigens / genetics*
  • Codon, Nonsense
  • Female
  • Frameshift Mutation
  • Humans
  • Neoplasm Proteins / genetics*
  • Pregnancy
  • Prevalence
  • Roma / genetics
  • Roma / statistics & numerical data
  • Uric Acid / blood

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Blood Group Antigens
  • Codon, Nonsense
  • Neoplasm Proteins
  • Uric Acid