COMPLEX LANDSCAPES OF SOMATIC REARRANGEMENT IN HUMAN BREAST CANCER GENOMES

By Philip J. Stephens, D. Mcbride, Meng‐Lay Lin, I. Varela, E. Pleasance, Jared T. Simpson, L. Stebbings, Catherine Leroy, S. Edkins, L. Mudie and 23 more. Nature, 2009

860 citations recorded by the source corpus.

Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.

Subfields: Cancer Research, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/02cb5d177a7c159c31485e08792f9073f4262e56

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Citations in the corpus

The DNA damage response and cancer therapy (2012, background): “For example, homologous-recombination deficient tumours have a characteristic mutational spectrum defined by the use of error-prone DSB repair mechanism”
Triple Negative Breast Cancer Cell Lines: One Tool in the Search for Better Treatment of Triple Negative Breast Cancer (2010, background): “The average number of rearrangements was higher in the cell lines than in the primary tumors [56].”
Mutational Processes Molding the Genomes of 21 Breast Cancers (2012, methodology): “Structural variants were called from the short insert data by using MAQ alignments as previously described (Campbell et al., 2008; Stephens et al., 2009).”
T Cell Dysfunction in Cancer (2018, background): “Introduction Tumors harbor genetic alterations resulting from DNA damage, e.g., due to exposure to UV light, tobacco smoke, or deficiencies in DNA repair (Alexandrov et al., 2013; Stephens et al., 2009).”
Advances in understanding cancer genomes through second-generation sequencing (2010, background): “Alternative, lower-cost approaches include shotgun sequencing with incomplete coverage (for example, less than 30-fold coverage; see below) — which is sufficient to identify somatic rearrangements in the genom”
SvABA: genome-wide detection of structural variants and indels by local assembly (2018, background): “Large events (>10 kbp) and inter-chromosomal translocations are rare in the germ-line due to stringent selection against gene dosage imbalance, but are prevalent in cancer, where genomes are often unstable and suffer frequent complex events (Stephens et al. 2009).”
Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development (2011, background): “Massively Parallel Sequencing The protocols for massively parallel, paired-end sequencing to identify somatically acquired genomic rearrangements in cancer samples have been described in detail elsewhere (Campbell et al., 2008; Quail et al., 2008; Stephens et al., 2009).”
A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? (2011, background): “…MRE levels due to misplacement and consequent altered expression of UTRs (Figure 3). ceRNA perturbation could also occur as a consequence of somatic genomic rearrangements affecting noncoding regions, which are emerging as hitherto unappreciated events in many cancers (Stephens et al., 2009).”