Anaplastic lymphoma kinase (ALK): A potential oncogenic driver in triple-negative breast cancer?

Abstract

1067 Background: TNBC, a molecularly heterogeneous subset of breast cancer, has an aggressive clinical course and no established targets for therapy. Wild-type ALK gene amplification by fluorescence in situ hybridization (FISH) was noted in 6/9 inflammatory TNBC specimens (Robertson et al. SABCS, P3-01-18). The status of ALK, full-length or fused, in non-inflammatory TNBC has not been described. Identification of a biomarker such as ALK in TNBC would be clinically significant, given the ongoing development of multiple ALK inhibitors. We screened for ALK expression in TNBC specimens with a novel patented qRT-PCR assay (Insight ALK Screen). Methods: We tested archived formalin-fixed, paraffin-embedded blocks of TNBC tissue. Evaluable specimens had sufficient tumor material for 10 slides with 5-micron sections. Insight ALK Screen was performed using previously described methodology (Hout, et al. AACR 2011, Abstract 2220). We subjected ALK Screen positive specimens to ALK break-apart FISH (Vysis) and direct sequencing analysis. Results: See clinical characteristics (Table). Insufficient RNA: 8/40 (20%). Insight ALK Screen-positive: 8/32 (25%). Break-apart FISH performed on these 8 specimens suggested 3/8 to be positive for ALK translocation and 2/8 to contain amplification of ALK without a translocation. The ALK-amplified specimens were subsequently confirmed with sequencing of RNA-PCR products to express full-length ALK. One additional ALK Screen-positive, FISH-negative specimen had full-length ALK expression confirmed on sequencing. Further analysis of the other 2 ALK Screen-positive cases is pending. Conclusions: ALK expression was seen in ~25% of TNBC specimens screened by Insight ALK Screen. We observed both ALK translocations and amplification/overexpression of full-length ALK. We are testing additional specimens by FISH and immunohistochemistry to evaluate the full spectrum of ALK alterations in TNBC. Updated data will be presented. [Table: see text]