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RESEARCH PRODUCT

Abstract 5379: Recurrent inactivation of PARD3, a polarity-related gene, in squamous cell carcinomas of the lung.

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Abstract In spite of the recent advances in cancer genomics, the genetics underlying the development of lung squamous cell carcinomas (SCC) is still poorly understood. Here, we investigated the contribution of the cell polarity-related gene, PARD3, to lung SCC carcinogenesis. First, we tested for PARD3 alterations in lung cancer cell lines from various histopathological types. The analysis confirmed an intragenic deletion at the H157 cells and unveiled biallelic mutations in another cell line. Both cell lines are SCCs, which circumscribed PARD3 alterations to this lung cancer type. Next, we extended the genetic screening, which included the determination of mutations and of intragenic deletions by multiplex ligation-dependent probe amplification (MLPA) assay, to lung primary SCCs. Overall, our analysis found that eight per cent of the 125 lung SCCs tested, endured biallelic and tumor-specific alterations at PARD3. The absence of PAR3 protein was evident in those tumors carrying frameshift-type mutations or intragenic deletions, while abnormally high immunostaining of PAR3 was observed in some PARD3 wild type tumors, suggesting positive feedback mechanisms. Further, we demonstrate that, as compared to the wild type, PAR3 mutant proteins were not able to significantly reduce cell growth, restore the appropriate formation of tight junctions or regulate downstream targets, evidencing the lack of function of these mutations. In conclusion, here we report, for the first time, the presence of recurrent and deleterious mutations at PARD3 in lung primary SCCs, which attest to its relevance in the development of lung SSCs. Citation Format: Ester Bonastre, Ilse Zondervan, Federica Facchinetti, Enric Condom, Suvi Savola, Julian Carretero, David Sidransky, Luca Roz, Elisabeth Brambilla, Montse Sanchez-Cespedes. Recurrent inactivation of PARD3, a polarity-related gene, in squamous cell carcinomas of the lung. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5379. doi:10.1158/1538-7445.AM2013-5379