Integrative transcriptome-wide analyses reveal critical HER2-regulated mRNAs and lincRNAs in HER2+ breast cancer

Breast Cancer Research and Treatment
Callie R MerryAhmad M Khalil

Abstract

Breast cancer is a major health problem affecting millions of women worldwide. Over 200,000 new cases are diagnosed annually in the USA, with approximately 40,000 of these cases resulting in death. HER2-positive (HER2+) breast tumors, representing 20-30 % of early-stage breast cancer diagnoses, are characterized by the amplification of the HER2 gene. However, the critical genes and pathways that become affected by HER2 amplification in humans are yet to be specifically identified. Furthermore, it is yet to be determined if HER2 amplification also affects the expression of long intervening non-coding (linc)RNAs, which are involved in the epigenetic regulation of gene expression. We examined changes in gene expression by next generation RNA sequencing in human tumors pre- and post- HER2 inhibition by trastuzumab in vivo, and changes in gene expression in response to HER2 knock down in cell culture models. We integrated our results with gene expression analysis of HER2+ tumors vs matched normal tissue from The Cancer Genome Atlas. The integrative analyses of these datasets led to the identification of a small set of mRNAs, and the associated biological pathways that become deregulated by HER2 amplification. Furthermore, our analys...Continue Reading

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Jun 29, 2018·The Journal of Clinical Investigation·Sabrina RizzolioLuca Tamagnone
Jan 8, 2019·Clinical Genetics·Carolina MathiasJaqueline C de Oliveira
Sep 5, 2017·Cancer Biomarkers : Section a of Disease Markers·Tianhe ZhaoZunzhen Zhang
Jun 19, 2019·Journal of Cellular Biochemistry·Mostafa KeshavarzAli Riahi-Madvar

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