title: Detection of redundant fusion transcripts as biomarkers or disease-specific therapeutic targets in breast cancer.
abstract: Fusion genes and fusion gene products are widely employed as biomarkers and therapeutic targets in hematopoietic cancers, but their applications have yet to be appreciated in solid tumors. Here, we report the use of SnowShoes-FTD, a powerful new analytic pipeline that can identify fusion transcripts and assess their redundancy and tumor subtype-specific distribution in primary tumors. In a study of primary breast tumors, SnowShoes-FTD was used to analyze paired-end mRNA-Seq data from a panel of estrogen receptor (ER)(+), HER2(+), and triple-negative primary breast tumors, identifying tumor-specific fusion transcripts by comparison with mRNA-Seq data from nontransformed human mammary epithelial cell cultures plus the Illumina Body Map data from normal tissues. We found that every primary breast tumor that was analyzed expressed one or more fusion transcripts. Of the 131 tumor-specific fusion transcripts identified, 86 were "private" (restricted to a single tumor) and 45 were "redundant" (distributed among multiple tumors). Among the redundant fusion transcripts, 7 were unique to ER(+) tumors and 8 were unique to triple-negative tumors. In contrast, none of the redundant fusion transcripts were unique to HER2(+) tumors. Both private and redundant fusion transcripts were widely expressed in primary breast tumors, with many mapping to genomic loci implicated in breast carcinogenesis and/or risk. Our finding that some fusion transcripts are tumor subtype-specific suggests that these entities may be critical determinants in the etiology of breast cancer subtypes, useful as biomarkers for tumor stratification, or exploitable as cancer-specific therapeutic targets.
authors.affiliation: Division of Biomedical Statistics and Bioinformatics, Mayo Clinic Rochester, Rochester, Minnesota, USA.
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: Brian M
authors.initials: BM
authors.lastname: Necela
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Kalari
authors.forename: Asif
authors.initials: A
authors.lastname: Hossain
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: Baker
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Carr
authors.forename: Caroline
authors.initials: C
authors.lastname: Davis
authors.forename: Julie E
authors.initials: JE
authors.lastname: Getz
authors.forename: Galen
authors.initials: G
authors.lastname: Hostetter
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Sarah A
authors.initials: SA
authors.lastname: McLaughlin
authors.forename: Derek C
authors.initials: DC
authors.lastname: Radisky
authors.forename: Gary P
authors.initials: GP
authors.lastname: Schroth
authors.forename: Heather E
authors.initials: HE
authors.lastname: Cunliffe
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005821:Genetic Techniques; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D012984:Software
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen