The acknowledged heterogeneity of breast cancer both at the clinical and at the molecular level has been a challenge in classification of breast cancer. This study aimed at identifying distinct molecular subgroups of the disease.
By using data from high resolution microarrays measuring copy number variation throughout the genome, two objective measurements were defined. A combination of these were used to group almost 600 breast carcinomas into four main groups, each further subdivided into two groups. Comparison with other molecular alterations at the DNA, RNA and protein level from the tumors showed that the groups had different characteristics; this was also reflected by distinct clinical profiles including differences in survival. As separate works, the relationship between molecular subgroups and methylation alterations, allele-specific genomic variation and bilateral disease were examined.
This work illustrates that the heterogeneity of breast carcinomas can be explained by distinct molecular alterations. It also shows the importance of platform independent algorithms; by merging data from different cohorts to obtain a large sample set, clinical relevant subgroups can be identified.
List of papers
Paper I: Paired distribution of molecular subtypes in bilateral breast carcinomas Hege G. Russnes, Ekatherina Sh. Kuligina, Evgeny N. Suspitsin, Ekaterina S. Jordanova, Cees J. Cornelisse, Anne-Lise Børresen-Dale, Evgeny N. Imyanitov Under review, Molecular Oncology
Paper II: Genomic architecture characterizes tumor progression paths and fate in breast cancer patients Hege G. Russnes, Hans Kristian Moen Vollan, Ole Christian Lingjærde, Alexander Krasnitz, Pär Lundin, Bjørn Naume, Therese Sørlie, Elin Borgen, Inga H. Rye, Anita Langerød, Suet-Feung Chin, Andrew E. Teschendorff, Philip J. Stephens, Susanne Månér, Ellen Schlichting, Lars O. Baumbusch, Rolf Kåresen, Michael P. Stratton, Michael Wigler, Carlos Caldas, Anders Zetterberg, James Hicks, Anne-Lise Børresen-Dale Submitted, Nature Medicine Sci Transl Med. 2010 Jun 30;2(38):38ra47. DOI: 10.1126/scitranslmed.3000611
Paper III: Subtype dependent alterations of the DNA methylation landscape in breast cancer and implications for prognosis Sitharthan Kamalakaran, Hege G. Russnes, Angel Janevski, Dan Levy, Jude Kendall, Vinay Varadan, Michael Riggs, Nilanjana Banerjee, Marit Synnestvedt, Ellen Schlichting, Rolf Kåresen, Robert Lucito, Michael Wigler, Nevenka Dimitrova, Bjørn Naume, Anne-Lise Børresen-Dale, James B. Hicks Manuscript
Paper IV: Novel tool reveals Allele Specific Copy number Aberrations in Tumors (ASCAT) Peter Van Loo, Silje H. Nordgard, Ole Christian Lingjærde, Hege G. Russnes, Inga H. Rye, Wei Sun, Victor J. Weigman, Peter Marynen, Anders Zetterberg, Charles M. Perou, Bjørn Naume, Anne-Lise Børresen-Dale, Vessela N. Kristensen Submitted, Nature Biotechnology