title: 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 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.
authors.affiliation: National Institute of Blood Transfusion (INTS), Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Saison
authors.forename: Virginie
authors.initials: V
authors.lastname: Helias
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Ballif
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.forename: Hervé
authors.initials: H
authors.lastname: Puy
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Sébastien
authors.initials: S
authors.lastname: Perrot
authors.forename: Muriel
authors.initials: M
authors.lastname: Vayssier-Taussat
authors.forename: Mauro
authors.initials: M
authors.lastname: Waldner
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Le Pennec
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cartron
authors.forename: Lionel
authors.initials: L
authors.lastname: Arnaud
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D001789:Blood Group Antigens / Q000235:genetics*; D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D011247:Pregnancy; D015995:Prevalence; D006178:Romani People / Q000235:genetics / Q000706:statistics & numerical data; D014527:Uric Acid / Q000097:blood
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001789:Blood Group Antigens; D018389:Codon, Nonsense; D009363:Neoplasm Proteins; D014527:Uric Acid