Fusion Breast Tumor Recurrence Risk, Genomic Instability

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Tumors’ RNA fusion transcripts appear to be a promising biomarker of genomic instability and prognostic factors.
Tumors’ RNA fusion transcripts appear to be a promising biomarker of genomic instability and prognostic factors.

SAN ANTONIO—Tumors' RNA fusion transcripts—chimeric RNA coded by genes that have undergone a fusion mutation—appear to be a promising biomarker of genomic instability and prognostic factors, according to E. Aubrey Thompson, PhD, of the Mayo Clinic Comprehensive Cancer Center in Jacksonville, FL.

Transcript analyses of RNA-sequence data for 813 breast tumors from The Cancer Genome Atlas project detected 2514 RNA fusion transcripts, Dr Thompson reported at the 2015 San Antonio Breast Cancer Symposium.1

“We conclude that, consistent with other observations, breast tumors generally exhibit a high level of genomic instability, associated with multiple copy number alterations and multiple fusion transcripts,” reported Dr Thompson.  

“Given the increasing emphasis on transcript profiling of clinical samples and the clinical significance of high risk Luminal A tumors, it may be timely to consider inclusion of fusion transcripts in such analyses as surrogate markers of genomic instability and potential therapeutic and/or prognostic indicators.”

Luminal A tumors with fusions represent a different subclass of tumors from Luminal A tumors without fusions, with “distinct molecular profiles, higher proliferation, higher genomic instability, higher risk of recurrence scores,” Dr Thompson said. For example, fusions were more frequent in recurrent Luminal A tumors than primary tumors (P = .0004), Dr Thompson reported.

Luminal A tumors harboring multiple fusion transcripts also had significantly more copy number aberrations “and were enriched for expression of mitotic cell cycle genes, characteristic of the recently described high risk CNH subclass of Luminal A tumors,” Dr Thompson said.

RELATED: Sequential Biopsies, Multi-Level Molecular Profiling Offer Important Insights into Tumor Evolution

“However, recurrence of specific fusion transcripts is low,” Dr Thompson noted. “About half of Luminal A tumors express fusion transcripts; and these tumors exhibit multiple copy number events, consistent with high level genomic instability, as well as enriched expression of mitotic cell cycle genes. These tumors appear to be related to the relatively high risk Luminal A CNH subclass, and express high levels of aurora kinases and polo-like kinases, which might be considered as therapeutic targets.”

Reference

  1. Thompson EA, Asmann YW, Su X, et al. A comprehensive analysis of fusion transcripts in breast cancer reveals associations between number of fusion transcripts, copy number events, gene expression profiles, and potentially clinical outcome. Oral presentation at: San Antonio Breast Cancer Symposium 2015; December 10, 2015; San Antonio, TX.

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