Integrated Analysis of the Gene Expression Profiling and Copy Number Aberration of the Ovarian Cancer

574 Background: FFPE is a valuable and widely available resource for translational research which to date has been under-used due to technical limitations. Improvement in technology has enabled genome-wide analysis of FFPE samples. We have assessed gene expression and copy number changes in the same cohort of breast cancers to identify markers or pathways important in prediction of treatment response. Methods: FFPE tissues from patients treated with neoadjuvant adriamycin/cyclophosphamide followed by taxanes in a clinical study were used. Gene expression profiling was assessed using the cDNA mediated annealing selection and ligation assay using the cancer panel which assess 502 genes (DASL assay, Illumina). Data was analysed using BeadStudio software. Copy number changes were assessed using the Molecular inversion probe assay with the 50K SNP panel (Affymetrix, California) and analysed using Nexus software (Biodiscovery). Results: Gene expression profiling was carried out on 44 samples. 12/44 (27%) patients had a pathological complete response (pCR) following chemotherapy. Significant differential expression of genes between pCR and non-pCR cancers were shown. TNFRSF5, CTSD, BCL3, ARNT, BIRC3, TGFBR1, MLLT6, and EVI2A were over-expressed and COL18A1, FGF12, IGFBP1 and NOTCH4 which were down-regulated in cancers that have a pCR (p ≤ 0.01). Copy number changes were assessed in 33 samples and comparison of copy number changes in pCR vs. non-pCR showed gains in regions 6q22, 21q21, 4p14, 4q21, 4p14, and loss at 11q11 (p ≤ 0.01). Three regions containing microRNA coding sequences, mir130a (11q11) mir142 (17q23) and mir21 (17q23) showed significant loss among pCR tumours (p < 0.05). Conclusions: This feasibility study shows that FFPE can be used for gene expression and copy number analysis which is a useful tool for the discovery of predictive markers for treatment response in neoadjuvant treatment trials. The role of TNFRSF5, microRNA 21/130a/142, and 11q11 loss should be further investigated as predictive markers of response to chemotherapy. [Table: see text]

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The potential role of IGF1r in young adult patients with gastroinetstinal stromal tumor (GIST)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.10562 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 10562-10562

Author(s):

M. Pantaleo ◽

A. Astolfi ◽

M. Di Battista ◽

P. Paterini ◽

D. Santini ◽

...

Keyword(s):

Gene Expression ◽

Young Adult ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Copy Number ◽

Adult Patients ◽

The Other ◽

Gene Copy ◽

Gastric Gist ◽

Array Analysis

10562 Background: The insulin-like growth factor 1 receptor (IGF1r) is a tyrosine kinase receptor that plays a key role in the growth of normal tissues. The aberration of IGF system has been found in many cancers. Some interesting results about IGF1r were published on GISTs. However, until now the real role on the pathogenesis of this disease and its clinical implications still needs to be defined. Methods: We studied IGF1r in 8 patients affected by gastric GIST. Seven patients underwent surgery at diagnosis, whereas one patient was operated after imatinib and sunitinib treatment. Two patients were young (< 30 years old), and other patients ranged between 54 and 85 years. IGF1r was studied as gene expression profiling performed with Affymetrix GeneChip HG-U133 Plus 2.0 arrays, as genomic copy number with SNP array analysis Affymetrix Genome Wide Human SNP 6.0 arrays, and with western blotting (WB) usinganti-IGF-IRβ (Santa Cruz Biotechnology). Results: The unsupervised analysis of gene expression profiling of our patients merged with a data set from a gastric GIST identified two groups with different regulation of IGF1r (FDR threshold to 0.2%). In particular, IGF1r was up-regulated in the two youngest patients (28 and 30 years-old). The SNPs array analysis gene copy number showed that none of the patients bore IGF1r amplification. The quantitative analysis of protein level by WB again showed that only the two youngest patients had an over-expression of IGF1r. In all the other patients the WB analysis was negative. Conclusions: These results suggest that IGF1r seems to be a novel signalling pathway other than KIT and PDGFRA in a subset of GISTs. The young adult patients had a strongly different molecular background in comparison to the other older ones. The correlation between IGF1r and mutational status of KIT and PDGFRA, clinical outcome, treatments responsiveness as well as its role as potential target deserves to be further investigated. No significant financial relationships to disclose.

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