Abstract 09: Laminin binding integrin copy number variations in distinct types of epithelial cancers
Authors: Erika Pond, William L. Harryman, Anne E. Cress
Journal: Clinical Cancer Research (2016)

Abstract Background: The laminin binding integrin (LBI) family are adhesion molecules that are essential for invasion and metastasis of human epithelial cancers and cell adhesion mediated drug resistance. Our objective was to investigate whether copy number variation (CNV) of a five gene signature (ITGB4, ITGA3, LAMB3, PLEC and SYNE3) comprised of essential genes for laminin adhesion would correlate with the reported clinical outcome in human epithelial tumors. Methods: We investigated the relative alteration frequency of the CNV of integrin B4 (ITGB4), integrin A3 (ITGA3), laminin beta 3 chain (LAMB3), plectin (PLEC) and nesprin 3 (SYNE3) as a five gene signature independent of the epithelial cancer type using the publically available and published data. Provisional data was excluded from the analysis. We rank ordered the results using a 20% alteration frequency cut off and limited the analysis to studies containing at least 100 samples. The Kaplan Meier survival curves were analyzed to determine any alterations in patient survival in terms of months. Results: Eight different cancer types representing 1,985 samples, contained at least a 20% alteration frequency of the five gene signature. The frequency of alteration ranged from 32.2% to 22.9% with the rank order (highest to lowest) as skin cutaneous melanoma, ovarian serous adenocarcinoma, stomach adenocarcinoma, lung adenocarcinoma, bladder urothelial carcinoma, breast invasive carcinoma and uterine corpus endometrial carcinoma. Within the gene signature, PLEC was the most commonly altered followed by LAMB3, ITGB4, ITGA3 and SYNE3 across all eight cancer types. Although specific mutations occurred in PLEC, amplification was the most common feature. Within a cancer type, there was little overlap of the individual amplified genes with the specific case, suggesting different specific amplicons may alter the LBI adhesion structures. Of the eight cancer types, a significant alteration in survival was indicated in bladder urothelial carcinoma (p=0.052714) with a median survival change of 19.02 to 24.28 months. Conclusions: A five gene signature was created representing the essential and genetically verified functional components of laminin binding integrins and their adhesion structures. The CNV signature of the laminin binding integrins may have prognostic and predictive significance depending on the type of epithelial cancer. These may be promising biomarkers but also rational targets for personalized therapy in selected epithelial tumors for preventing metastatic spread. (Supported in part by NIH grants CA 23074 and CA 159406) Citation Format: Erika Pond, William L. Harryman, Anne E. Cress. Laminin binding integrin copy number variations in distinct types of epithelial cancers. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 09.