Abstract LB-A08: ALK and ROS-1 status: A retrospective analysis in solid tumors

Abstract

Abstract Background: Tyrosine kinase receptors are important regulators of cellular signal transduction pathways that play a crucial role in development of cancer. Among them, Anaplastic Lymphoma Kinase (ALK) and C-Ros Oncogene-1 (ROS-1) are activated by rearrangement in several tumors. Tailored therapies have been developed according to the status of ALK and ROS-1, successfully used in NSCLC and potentially useful in other solid tumors harboring ALK and ROS-1 aberrations. Material and methods: ALK and ROS-1 status was evaluated in 666 and 441 patients with solid tumors, respectively, since 2014 at the Pathology Department. ALK and ROS-1 rearrangement and gene copy number variation (CNV) were assayed by fluorescence in situ hybridization (FISH). Gene copy number gain was defined by 3 to 5 fusion signals on average in ≥10% of cells, with amplification being highlighted by the clusters or 10 to 15 fusion signals in 10% or more tumor cells. Results: ALK status was assessed in 650/666 (97%) cases, while ROS-1 status was evaluable in 426/441 (96%). We identified 15/650 (2.3%) cases with ALK rearrangment, including 13 lung adenocarcinomas (4.1%), 1 colon cancer (0.5%) and 1 myoepithelioma (0.5%). CNV for ALK was documented in 53% lung adenocarcinoma, 50% pancreatic, 41% biliary and 37% colon carcinoma patients. We found 7/426 (1.6%) tumors with ROS-1 rearrangement, corresponding to 5 lung (2.7%) and 2 colon (1.3%) adenocarcinomas. CNV for ROS-1 was more frequent in melanoma (77%), neuroendocrine tumors (39%) and NSCLC (32%, 3/4 cases of ROS-1 amplification were squamous carcinoma). Eight out of the 22 rearranged cases (5 ALK and 3 ROS-1) were tested for both genes: these aberrations were mutually exclusive. Three out of 5 (60%) ALK rearranged tumors showed ROS-1 deletion. No ALK and ROS-1 alterations were documented in 30 pancreatic, 25 H&N, 22 biliary tract, 13 renal, and 13 breast carcinomas, as well as in 13 melanomas and 36 other solid tumors. Conclusions: ALK and ROS-1 rearrangement was found in 4.1% and 2.7% of NSCLC, respectively, in keeping with literature data. In other solid tumors, the percentage of rearrangements is exceedingly low, but melanoma, neuroendocrine tumors, pancreatic and colon cancer may show significant CNV. We speculate that such aberrations of ALK and ROS-1 could act as potential therapy targets, but additional investigation by immunohistochemistry and next generation sequencing is clinically warranted. Citation Format: Maria Silvia Cona, matteo Duca, Adele Testi, Sara Cresta, Katia Fiorella Dotti, Alice Indini, Diego Signorelli, Giuseppe Pelosi, Filippo Guglielmo de Braud, Silvia Damian. ALK and ROS-1 status: A retrospective analysis in solid tumors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-A08.