title: Transcriptional consequences of genomic structural aberrations in breast cancer.
abstract: Using a long-span, paired-end deep sequencing strategy, we have comprehensively identified cancer genome rearrangements in eight breast cancer genomes. Herein, we show that 40%-54% of these structural genomic rearrangements result in different forms of fusion transcripts and that 44% are potentially translated. We find that single segmental tandem duplication spanning several genes is a major source of the fusion gene transcripts in both cell lines and primary tumors involving adjacent genes placed in the reverse-order position by the duplication event. Certain other structural mutations, however, tend to attenuate gene expression. From these candidate gene fusions, we have found a fusion transcript (RPS6KB1-VMP1) recurrently expressed in ∼30% of breast cancers associated with potential clinical consequences. This gene fusion is caused by tandem duplication on 17q23 and appears to be an indicator of local genomic instability altering the expression of oncogenic components such as MIR21 and RPS6KB1.
authors.affiliation: Cancer Biology and Pharmacology, Genome Institute of Singapore, Genome, Singapore 138672, Singapore.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Inaki
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.forename: Leena
authors.initials: L
authors.lastname: Ukil
authors.forename: Fei
authors.initials: F
authors.lastname: Yao
authors.forename: Xing Yi
authors.initials: XY
authors.lastname: Woo
authors.forename: Leah A
authors.initials: LA
authors.lastname: Vardy
authors.forename: Kelson Folkvard Braaten
authors.initials: KF
authors.lastname: Zawack
authors.forename: Charlie Wah Heng
authors.initials: CW
authors.lastname: Lee
authors.forename: Pramila Nuwantha
authors.initials: PN
authors.lastname: Ariyaratne
authors.forename: Yang Sun
authors.initials: YS
authors.lastname: Chan
authors.forename: Kartiki Vasant
authors.initials: KV
authors.lastname: Desai
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Thomas Choudary
authors.initials: TC
authors.lastname: Putti
authors.forename: Wai Loon
authors.initials: WL
authors.lastname: Ong
authors.forename: Atif
authors.initials: A
authors.lastname: Shahab
authors.forename: Valere
authors.initials: V
authors.lastname: Cacheux-Rataboul
authors.forename: Radha Krishna Murthy
authors.initials: RK
authors.lastname: Karuturi
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Sung
authors.forename: Xiaoan
authors.initials: X
authors.lastname: Ruan
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bourque
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D015894:Genome, Human / Q000235:genetics*; D042822:Genomic Instability; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C526584:VMP1 protein, human; D019893:Ribosomal Protein S6 Kinases