Abstract 4922: Analysis of copy number changes in HNSCC by MLPA

Gene amplification is a common finding in a broad spectrum of tumor types, often leading to increased levels of gene expression, a mechanism by which genetic changes contribute to the initiation or progression of cancer. HNSCC is among the neoplasias that frequently show amplification of specific genomic regions. Previous cytogenetic and molecular genetic studies by Fluorescence in situ Hybridization (FISH) and comperative genome hybridization (CGH) and other molecular methods showed that frequently amplified chromosomal regions in primary HNSCC tumors are 3q, 8q, 8p, 11q, 9q. Generally, proto-oncogenes reside in these amplified regions and amplification of these often leads to increased levels of gene expression. Therefore, in this study we investigated amplification of 22 different oncogenes mapping to these regions. The analyses were performed by MLPA on an ABI 3100 genetic analyzer and relative peak areas of the amplification products were evaluated using the Coffalyser MLPA analysis software. Analysis of 50 HNSCC tumor tissue samples showed that the most frequently amplified genes were from the regions 17q12 (MED1), 11q13.3 (CCND1), 8q (MYC and MTDH) and 8p (ZNF703) with frequencies of 24%, 24%, 20%, 20% and 18%, respectively. In total, Copy Number Alterations of the CCND1 and MED1 genes were observed in 12 of 50 tumor samples. For the CCND1 gene 6 of these alterations were heterozygous duplications and the remaining 6 were triplications. On the other hand, for the MED1 gene duplications were observed in 8 samples and trriplications were detected in 4 samples. Triplication of the MTDH gene was not observed in any of the amplified samples. However, one third of the ZNF703 amplifications were triplications. Amplification of the CCND1 and MYC genes are frequently observed in different types of cancers including HNSCC. More recently overexpression of MTDH has been associated with lymph node metastasis and poor-survival in HNSCC. However, to our knowledge there is no data in the literature investigating the ZNF703 gene in HNSCC. Our data indicate that ZNF703 may represent a candidate gene the role of which warrants more detailed analysis in HNSCC. Citation Format: Nejat Dalay, Orkun Gurbuz, Elif Baltaci, Emin Karaman, Nur Buyru. Analysis of copy number changes in HNSCC by MLPA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4922. doi:10.1158/1538-7445.AM2015-4922