Abstract 5346: Tumor cell heterogeneity and chromosomal abnormality in malignant pleural effusion (MPE) samples of lung cancer

Abstract

Abstract Tumor heterogeneity is a hallmark of cancer and different types and stages of cancer express various cell surface markers and gene expression profiles. To understand tumor cell heterogeneity in lung cancer, we have developed a model using primary cells from malignant plural effusion (MPE) from lung cancer patients. Using this system we have identified CD44high expressing primary tumor cells within the MPE that form colonies in soft agar in vitro, and tumors in SCID/NOD mice. RT-PCR analysis revealed higher expression of cancer stem cell markers, Bmi-1, hTERT, EZH2, and OCT-4 in CD44high cells than the CD44low cells. Thus, our results indicate that primary tumor cells of MPE derived from lung cancer patients show heterogeneity with respect to their tumorigenic potential. To determine whether we could detect cytogenetic abnormalities in these samples, we performed karyotypic analysis of the MPE samples. Fibroblast cell line GM 05399 served as a control for these studies. Hyperdiploidy was observed in all three MPE samples and in the control cell line H 2122. Abnormalities of chromosome 1p were observed seen in all the samples that led us to perform FISH (fluorescence in situ hybridization) studies using a dual color 1p36 and 1q25 probe (control). We found LOH (loss of heterozygosity) at 1p36 in two MPE samples and rearrangements of both 1p/1q regions in the third MPE sample. Cell line H 2122 contained one normal chromosome 1 and an unbalanced translocation of unknown origin at 1p36 consistent with deletion of 1p. Our studies therefore suggest that this 1p36 deletion could result in the inactivation of a tumor suppressor gene and other sequences that include miRNA 34a also mapped to this locus. Chromosomal rearrangements further indicate that cells with multiple phenotypes including those related to metastasis, and chemo-radiation resistance might be present in the MPE samples. These studies provide a good basis suggesting that MPE would serve as a useful model system for the identification of genes related to the progression of lung cancer. 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 5346. doi:1538-7445.AM2012-5346