A256: A study of the relationship between intratumor morphological heterogeneity and genetic changes in breast cancer

Evgeny Denisov1,2,Nikolay Skryabin3,Tatiana Gerashchenko1,2,Jochen Wilhelm4,Daria Pautova2,Marina Zavyalova1,2,Nadezhda Cherdyntseva1,2,Vladimir Perelmuter1

1Tomsk Cancer Research Institute, Tomsk, Russia,2Tomsk State University, Tomsk, Russia,3Institute of Medical Genetics, Tomsk, Russia,4Justus-Liebig-University Giessen, Giessen, Germany

Presenting date: Monday 2 November
Presenting time: 13.10-14.00

Background

Breast cancer (BC) shows significant intratumor morphological heterogeneity, which is represented by five types of morphological structures of tumor cells: tubular, alveolar, trabecular, solid structures, and discrete groups of tumor cells. Intratumor morphological heterogeneity was found to contribute to BC metastasis and chemoresistance. In the present study, we aimed whether intratumor morphological heterogeneity in BC is related to cytogenetic and gene expression changes in tumor cells.

Method

Five types of morphological structures were isolated from samples of invasive carcinoma of no special type (n=3) by laser microdissection. DNA and RNA samples were subjected to whole genome and transcriptome amplification and were used to perform genome-wide array CGH (SurePrint G3 Human CGH 8x60K) and transcriptome-wide array analysis (SurePrint G3 Human Gene Expression 8x60K v2, Agilent). In a case of DNA, three distinct regions of the primary tumor were laser microdissected; five types of morphological structures were obtained from each breast tumor region.

Results

The number of unbalanced chromosome aberrations is significantly not differed between morphological structures. No chromosome abnormalities specific for each type of morphological structures were observed. There was no similarity of the same structures from distinct tumor regions in chromosome abnormalities. We did not observe any patterns in clusterization of morphological structures by chromosome aberrations. Regarding transcriptome profiling it was found that discrete groups of tumor cells significantly differed in gene expression from other structures. Tubular structures were similar with solid structures, whereas trabecular - with alveolar structures. In each type of morphological structures, we found specific down- and up-regulated genes involved in different signaling pathways: tubular structures - GNRHR and nAChRs pathways, solid structures - angiogenesis and Wnt signaling pathways etc.

Conclusion

Intratumor morphological heterogeneity in BC is not related to chromosome aberrations, but it can be associated with the expression of specific genes.