Detection Of Vegfa Gene Amplification In Different Neoplastic Entities Using Four Different Technologies

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background The VEGFA protein plays an important role in the induction of angiogenesis during tumor initiation and progression. The aims of the study were to investigate the presence of VEGFA gene amplification by FISH analysis on a human multi-tumor tissue microarray (MTMA) and to validate these findings on an independent human multi-tumor tissue in mouse implanted microarray (MTMA) by aCGH, SNP6 microarrays, FISH analysis and real-time PCR. Materials and Methods The VEGFA gene status was evaluated on a human MTMA (n=2,957 tissue samples) including 132 tumor entities and 31 normal tissue types. Furthermore, we reconfirmed the presence of VEGFA gene amplification as detected by FISH analysis on a second independent MTMA including 195 different tissue samples from nude mice xenograft models of 24 different human tumor types using three additional genomic techniques: array-CGH, SNP6 microarrays and real-time PCR. Results VEGFA gene amplification was detected across different tumor types. The following incidences were observed: 5.3% in colorectal carcinoma, 3.2% in endometrial carcinoma, 2.8% in gallbladder adenocarcinoma, 4.2 % in renal carcinoma, 1.5% in hepatocellular carcinoma, 4.5% in pancreas carcinoma and 4.8% in stomach carcinoma samples. Additionally, some tumors were characterized by a high polysomy. In the second independent cohort MTMA VEGFA gene amplification was detected by FISH analysis in four samples, including one non-small cell lung cancer, one sarcoma, one gastric and and breast cancer, previously classified as amplified by aCGH (100%) and SNP6 microarrays. The latter technique also revealed one “supplementary amplified sample”. All results correlated with real-time PCR (p<0.05). Conclusions We detected VEGFA gene amplification in different tumor types, on a human MTMA and we confirmed our findings on an independent MTMA of human tumors implanted in mice. We demonstrated the occurrence of VEGFA gene amplification in several tumor types with an incidence of up to 5% and also we demonstrated the feasibility of four technologies for reliable VEGFA gene copy number detection. Comparison of the four technologies revealed high concordance (p<0.05). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5295. doi:1538-7445.AM2012-5295