Abstract P2-06-05: LINC00478: A novel tumor suppressor in breast cancer

Background: LncRNAs may play a role in cancer and serve as new potential targets for improving cancer diagnosis, prognosis or treatment. Long intergenic non-protein coding RNA 478 (LINC00478), the miR99a-let-7c cluster host gene, has been shown to be downregulated in estrogen-independent ER-positive (ER+) breast cancer cells. However, its expression in breast tumors and its significance in recurrence has not been well characterized. Methods: The clinical relevance of LINC00478 in ER+ breast tumors was first determined by analysis of the expression levels in MiTranscriptome database (RNAseq-based), which contains ∼8000 most differentially expressed lncRNAs for each cancer and/or tissue type. Additionally, the expression of LINC00478 mRNA was determined in a) a cohort of matched pairs of primary and (nodal) metastatic tumors (n=18) (RNA-seq) and b) a cohort of 60 paraffin-embedded ER-positive, node-negative breast carcinomas with Oncotype DX recurrence scores (QRT-PCR). Results: LINC00478 was significantly downregulated in patients with ER-positive tumors compared to uninvolved normal breast tissue. In RNA-seq analysis, metastatic tumors had significant low expression as compared to matched primary tumors (FC: -2.2 fold-down; P=0.0027). Quantitative RT-PCR analysis showed that LINC00478 expression was significantly lower in ER+ node-negative patients with Oncotype DX high recurrence score when compared with low recurrence score patients (FC: -4.14-fold down; P=0.02). Conclusion: We document for the first time that LINC00478 functions as a tumor suppressor in ER-positive breast cancer. Its loss is associated with tumor progression and recurrence/metastasis. Novel strategies that focus on re-expression of LINC00478 might be useful for targeting breast cancer and preventing the metastases. Citation Format: Gokmen-Polar Y, Zavodszky M, Chen X, Gu X, Kodira C, Badve S. LINC00478: A novel tumor suppressor in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-06-05.