Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution

Sohrab P. Shah, Ryan D. Morin, Jaswinder Khattra, Leah Prentice, Trevor Pugh, Angela Burleigh, Allen Delaney, Karen Gelmon, Ryan Guliany, Janine Senz, Christian Steidl, Robert A. Holt, Steven Jones, Mark Sun, Gillian Leung, Richard Moore, Tesa Severson, Greg A. Taylor, Andrew E. Teschendorff, Kane Tse, Gulisa Turashvili, Richard Varhol, René L. Warren, Peter Watson, Yongjun Zhao, Carlos Caldas, David Huntsman, Martin Hirst, Marco A. Marra () and Samuel Aparicio ()
Additional contact information
Sohrab P. Shah: Molecular Oncology,
Ryan D. Morin: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Jaswinder Khattra: Molecular Oncology,
Leah Prentice: Molecular Oncology,
Trevor Pugh: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Angela Burleigh: Molecular Oncology,
Allen Delaney: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Karen Gelmon: Medical Oncology, BC Cancer Agency, 600 West 10th Avenue, Vancouver V5Z 1L3, Canada
Ryan Guliany: Molecular Oncology,
Janine Senz: Centre for Translational and Applied Genomics,
Christian Steidl: Centre for Translational and Applied Genomics,
Robert A. Holt: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Steven Jones: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Mark Sun: Molecular Oncology,
Gillian Leung: Molecular Oncology,
Richard Moore: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Tesa Severson: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Greg A. Taylor: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Andrew E. Teschendorff: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
Kane Tse: Molecular Oncology,
Gulisa Turashvili: Molecular Oncology,
Richard Varhol: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
René L. Warren: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Peter Watson: Deeley Research Centre, BC Cancer Agency
Yongjun Zhao: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Carlos Caldas: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
David Huntsman: Centre for Translational and Applied Genomics,
Martin Hirst: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Marco A. Marra: Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver V5Z 1L3, Canada
Samuel Aparicio: Molecular Oncology,

Nature, 2009, vol. 461, issue 7265, 809-813

Abstract: A cancer evolves: heterogeneity and mutational evolution in a breast tumour Next-generation sequencing approaches have been used to investigate the genomes and transcriptomes of an oestrogen-receptor-α-positive metastatic lobular breast cancer from a patient — rather than from a cell line or xenograft — over a 9-year period between the diagnosis of the primary tumour and the appearance of metastasis. Comparison of the somatic non-synonymous coding mutations in the metastasis and the primary tumour of the same patient and the combined analysis of genome and transcriptome data provided insights into the mutational evolution that can occur with disease progression. The cover shows sequence elements of the HAUS3 locus, one of the genes found to be mutated in the tissue (shown in the background) from the primary lobular cancer used for this work.

Date: 2009
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DOI: 10.1038/nature08489

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