Papers

Peer-reviewed International journal
Nov 22, 2021

Transcript-targeted analysis reveals isoform alterations and double-hop fusions in breast cancer.

Communications biology
  • Shinichi Namba
  • Toshihide Ueno
  • Shinya Kojima
  • Kenya Kobayashi
  • Katsushige Kawase
  • Yosuke Tanaka
  • Satoshi Inoue
  • Fumishi Kishigami
  • Shusuke Kawashima
  • Noriko Maeda
  • Tomoko Ogawa
  • Shoichi Hazama
  • Yosuke Togashi
  • Mizuo Ando
  • Yuichi Shiraishi
  • Hiroyuki Mano
  • Masahito Kawazu
  • Display all

Volume
4
Number
1
First page
1320
Last page
1320
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1038/s42003-021-02833-4

Although transcriptome alteration is an essential driver of carcinogenesis, the effects of chromosomal structural alterations on the cancer transcriptome are not yet fully understood. Short-read transcript sequencing has prevented researchers from directly exploring full-length transcripts, forcing them to focus on individual splice sites. Here, we develop a pipeline for Multi-Sample long-read Transcriptome Assembly (MuSTA), which enables construction of a transcriptome from long-read sequence data. Using the constructed transcriptome as a reference, we analyze RNA extracted from 22 clinical breast cancer specimens. We identify a comprehensive set of subtype-specific and differentially used isoforms, which extended our knowledge of isoform regulation to unannotated isoforms including a short form TNS3. We also find that the exon-intron structure of fusion transcripts depends on their genomic context, and we identify double-hop fusion transcripts that are transcribed from complex structural rearrangements. For example, a double-hop fusion results in aberrant expression of an endogenous retroviral gene, ERVFRD-1, which is normally expressed exclusively in placenta and is thought to protect fetus from maternal rejection; expression is elevated in several TCGA samples with ERVFRD-1 fusions. Our analyses provide direct evidence that full-length transcript sequencing of clinical samples can add to our understanding of cancer biology and genomics in general.

Link information
DOI
https://doi.org/10.1038/s42003-021-02833-4
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34811492
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608905
ID information
  • DOI : 10.1038/s42003-021-02833-4
  • Pubmed ID : 34811492
  • Pubmed Central ID : PMC8608905

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