title: Novel insights into breast cancer genetic variance through RNA sequencing.
abstract: Using RNA sequencing of triple-negative breast cancer (TNBC), non-TBNC and HER2-positive breast cancer sub-types, here we report novel expressed variants, allelic prevalence and abundance, and coexpression with other variation, and splicing signatures. To reveal the most prevalent variant alleles, we overlaid our findings with cancer- and population-based datasets and validated a subset of novel variants of cancer-related genes: ESRP2, GBP1, TPP1, MAD2L1BP, GLUD2 and SLC30A8. As a proof-of-principle, we demonstrated that a rare substitution in the splicing coordinator ESRP2 (R353Q) impairs its ability to bind to its substrate FGFR2 pre-mRNA. In addition, we describe novel SNPs and INDELs in cancer relevant genes with no prior reported association of point mutations with cancer, such as MTAP and MAGED1. For the first time, this study illustrates the power of RNA-sequencing in revealing the variation landscape of breast transcriptome and exemplifies analytical strategies to search regulatory interactions among cancer relevant molecules.
authors.affiliation: McCormick Genomic and Proteomics Center, Washington, District of Columbia 20037, USA.
authors.forename: Anelia
authors.initials: A
authors.lastname: Horvath
authors.forename: Suresh Babu
authors.initials: SB
authors.lastname: Pakala
authors.forename: Prakriti
authors.initials: P
authors.lastname: Mudvari
authors.forename: Sirigiri Divijendra Natha
authors.initials: SD
authors.lastname: Reddy
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Ohshiro
authors.forename: Sandra
authors.initials: S
authors.lastname: Casimiro
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pires
authors.forename: Suzanne A W
authors.initials: SA
authors.lastname: Fuqua
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Luis
authors.initials: L
authors.lastname: Costa
authors.forename: Sujit S
authors.initials: SS
authors.lastname: Nair
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D023281:Genomics; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D012322:RNA Precursors; D000091346:Tripeptidyl-Peptidase 1; C000717267:TPP1 protein, human