title: Whole exome sequencing analysis of ABCC8 and ABCD2 genes associating with clinical course of breast carcinoma.
abstract: The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance.
authors.affiliation: Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. pavel.soucek@lfp.cuni.cz.
authors.forename: P
authors.initials: P
authors.lastname: Soucek
authors.forename: V
authors.initials: V
authors.lastname: Hlavac
authors.forename: K
authors.initials: K
authors.lastname: Elsnerova
authors.forename: R
authors.initials: R
authors.lastname: Vaclavikova
authors.forename: R
authors.initials: R
authors.lastname: Kozevnikovova
authors.forename: K
authors.initials: K
authors.lastname: Raus
mesh_terms: D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D064233:Sulfonylurea Receptors / Q000235:genetics*
chemical_list: C577507:ABCC8 protein, human; C431694:ABCD2 protein, human; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D064233:Sulfonylurea Receptors