Genome Remodeling in a Basal-like Breast Cancer Metastasis and Xenograft

By Li Ding, M. Ellis, Shunqiang Li, David E. Larson, Ken Chen, J. Wallis, C. Harris, M. McLellan, R. Fulton, L. Fulton and 59 more. Nature, 2010

1,204 citations recorded by the source corpus.

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.

Subfields: Cancer Research, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/a125cde146760b1e6630d452c359264a4a7cb87d

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Citations in the corpus

Mutational Processes Molding the Genomes of 21 Breast Cancers (2012, background): “The completion of the human genome sequence and the advent of second-generation sequencing technology have overcome historic limitations of scale, permitting sequencing of whole cancer genomes (Berger et al., 2011; Chapman et al., 2011; Ding et al., 2010; Lee et al., 2010; Ley et al., 2008; Mardis e”
VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. (2012, background): “The genomes of primary tumors are genetically heterogeneous (Ding et al. 2010), with frequent rearrangements (Campbell et al. 2008) and copy number alterations (CNAs) (Beroukhim et al. 2010).”
Cancer to bone: a fatal attraction (2011, neutral): “Genetically unstable tumour cells are exposed to clonal selection during the colonization of distant site”
Patient-derived tumor xenografts: transforming clinical samples into mouse models. (2013, background): “the human stromal compartment and interactions with the mouse stromal microenvironment (14, 17, 19).”
Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets (2015, background): “Because cancers are genetically heterogeneous (3-9), sampling a cancer in two different locations is expected to reveal mutations exclusive to each sample.”
The clonal and mutational evolution spectrum of primary triple-negative breast cancers (2012, background): “Weand othershaveshown 22,23 how deep-frequency measurements of allelic abundance can be used to study tumour clonal evolution.”
Metastatic Stem Cells: Sources, Niches, and Vital Pathways (2014, background): “, 2010), other than mutations in classic initiator oncogenes that are further enriched in metastatic lesions (Campbell et al., 2010; Ding et al., 2010).”