Novel insights into breast cancer genetic variance through RNA sequencing

Anelia Horvath, Suresh Babu Pakala, Prakriti Mudvari, Sirigiri Divijendra Natha Reddy, Kazufumi Ohshiro, Sandra Casimiro, Ricardo Pires, Suzanne A W Fuqua, Masakazu Toi, Luis Costa, Sujit S. Nair, Saraswati Sukumar, Rakesh Kumar

Research output: Contribution to journalArticle

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 MTAPand 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.

Original languageEnglish (US)
Article number2256
JournalScientific Reports
Volume3
DOIs
StatePublished - Jul 25 2013

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RNA Sequence Analysis
Neoplasm Genes
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms
Aptitude
Time and Motion Studies
RNA Precursors
Transcriptome
Point Mutation
Single Nucleotide Polymorphism
Breast
Alleles
Population

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Horvath, A., Pakala, S. B., Mudvari, P., Reddy, S. D. N., Ohshiro, K., Casimiro, S., ... Kumar, R. (2013). Novel insights into breast cancer genetic variance through RNA sequencing. Scientific Reports, 3, [2256]. https://doi.org/10.1038/srep02256

Novel insights into breast cancer genetic variance through RNA sequencing. / Horvath, Anelia; Pakala, Suresh Babu; Mudvari, Prakriti; Reddy, Sirigiri Divijendra Natha; Ohshiro, Kazufumi; Casimiro, Sandra; Pires, Ricardo; Fuqua, Suzanne A W; Toi, Masakazu; Costa, Luis; Nair, Sujit S.; Sukumar, Saraswati; Kumar, Rakesh.

In: Scientific Reports, Vol. 3, 2256, 25.07.2013.

Research output: Contribution to journalArticle

Horvath, A, Pakala, SB, Mudvari, P, Reddy, SDN, Ohshiro, K, Casimiro, S, Pires, R, Fuqua, SAW, Toi, M, Costa, L, Nair, SS, Sukumar, S & Kumar, R 2013, 'Novel insights into breast cancer genetic variance through RNA sequencing', Scientific Reports, vol. 3, 2256. https://doi.org/10.1038/srep02256
Horvath A, Pakala SB, Mudvari P, Reddy SDN, Ohshiro K, Casimiro S et al. Novel insights into breast cancer genetic variance through RNA sequencing. Scientific Reports. 2013 Jul 25;3. 2256. https://doi.org/10.1038/srep02256
Horvath, Anelia ; Pakala, Suresh Babu ; Mudvari, Prakriti ; Reddy, Sirigiri Divijendra Natha ; Ohshiro, Kazufumi ; Casimiro, Sandra ; Pires, Ricardo ; Fuqua, Suzanne A W ; Toi, Masakazu ; Costa, Luis ; Nair, Sujit S. ; Sukumar, Saraswati ; Kumar, Rakesh. / Novel insights into breast cancer genetic variance through RNA sequencing. In: Scientific Reports. 2013 ; Vol. 3.
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