Abstract P5-09-03: Expression of the C9Orf72 long-isoform in cancer tissues prognosticates disease-free and breast cancer-specific survival

Background: An expansion of the GGGGCC hexanucleotide repeat in C9Orf72 gene promoter results in reduced mRNA expression of its long-isoform, and has been associated with amyotrophic lateral sclerosis, and frontotemporal dementia. Over-expression of C9Orf72 in cultured neuronal cells resulted in increased cell death, but its role in oncogenesis and, specifically, in brain metastasis is unknown. Materials and Methods:C9Orf72 mRNA levels were measured by qPCR in 200 normal breast, 217 (cohort 1) and 100 (cohort 2) breast tumor samples, and correlated with clinico-pathological variables, breast cancer-specific (BCSS) and disease-free survival (DFS). MCF-7 tumor xenografts models were used to observe the effect of C9Orf72 on tumor metastasis. Results:C9Orf72 mRNA levels were statistically higher in tumor than in normal breast tissues (P Discussion:C9Orf72 low levels were highly specific and sensitive prognostic factors of worse DFS and BCSS in two demographically distinct cohorts of breast cancer patients, and increased C9Orf72 expression resulted in reduced metastatic events in a mouse xenograft model. The molecular mechanisms of C9Orf72-induced cell death are unknown and warrant deep investigation because of its possible association with brain metastasis. C9Orf72 has the potential to emerge as a very attractive prognostic biomarker and potential therapeutic candidate in breast cancers. Senior authors: RG, HAP. This work was partially funded by GlaxoSmithKline ERI grant. Citation Format: Nabila Chaher, Esha Madan, Clifford Qualls, Melanie Royce, Periannan Kuppusamy, Rajan Gogna, Hugo Arias-Pulido. Expression of the C9Orf72 long-isoform in cancer tissues prognosticates disease-free and breast cancer-specific survival [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-09-03.