Detection of redundant fusion transcripts as biomarkers or disease-specific therapeutic targets in breast cancer

Yan Asmann, Brian M. Necela, Krishna R Kalari, Asif Hossain, Tiffany R. Baker, Jennifer M. Carr, Caroline Davis, Julie E. Getz, Galen Hostetter, Xing Li, Sarah A. McLaughlin, Derek C Radisky, Gary P. Schroth, Heather E. Cunliffe, Edith A. Perez, E Aubrey Thompson

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1921-1928
Number of pages8
JournalCancer Research
Volume72
Issue number8
DOIs
StatePublished - Apr 15 2012

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Biomarkers
Breast Neoplasms
Neoplasms
Therapeutics
Estrogen Receptors
Breast
Messenger RNA
Gene Fusion
Tumor Biomarkers
Carcinogenesis
Cell Culture Techniques
Epithelial Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Detection of redundant fusion transcripts as biomarkers or disease-specific therapeutic targets in breast cancer. / Asmann, Yan; Necela, Brian M.; Kalari, Krishna R; Hossain, Asif; Baker, Tiffany R.; Carr, Jennifer M.; Davis, Caroline; Getz, Julie E.; Hostetter, Galen; Li, Xing; McLaughlin, Sarah A.; Radisky, Derek C; Schroth, Gary P.; Cunliffe, Heather E.; Perez, Edith A.; Thompson, E Aubrey.

In: Cancer Research, Vol. 72, No. 8, 15.04.2012, p. 1921-1928.

Research output: Contribution to journalArticle

Asmann, Y, Necela, BM, Kalari, KR, Hossain, A, Baker, TR, Carr, JM, Davis, C, Getz, JE, Hostetter, G, Li, X, McLaughlin, SA, Radisky, DC, Schroth, GP, Cunliffe, HE, Perez, EA & Thompson, EA 2012, 'Detection of redundant fusion transcripts as biomarkers or disease-specific therapeutic targets in breast cancer', Cancer Research, vol. 72, no. 8, pp. 1921-1928. https://doi.org/10.1158/0008-5472.CAN-11-3142
Asmann, Yan ; Necela, Brian M. ; Kalari, Krishna R ; Hossain, Asif ; Baker, Tiffany R. ; Carr, Jennifer M. ; Davis, Caroline ; Getz, Julie E. ; Hostetter, Galen ; Li, Xing ; McLaughlin, Sarah A. ; Radisky, Derek C ; Schroth, Gary P. ; Cunliffe, Heather E. ; Perez, Edith A. ; Thompson, E Aubrey. / Detection of redundant fusion transcripts as biomarkers or disease-specific therapeutic targets in breast cancer. In: Cancer Research. 2012 ; Vol. 72, No. 8. pp. 1921-1928.
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