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

By Sohrab P. Shah, Ryan D. Morin, J. Khattra, Leah M Prentice, Trevor J Pugh, A. Burleigh, Allen D. Delaney, K. Gelmon, Ryan Guliany, J. Senz and 20 more. Nature, 2009

1,143 citations recorded by the source corpus.

Recent advances in next generation sequencing have made it possible to precisely characterize all somatic coding mutations that occur during the development and progression of individual cancers. Here we used these approaches to sequence the genomes (>43-fold coverage) and transcriptomes of an oestrogen-receptor-α-positive metastatic lobular breast cancer at depth. We found 32 somatic non-synonymous coding mutations present in the metastasis, and measured the frequency of these somatic mutations in DNA from the primary tumour of the same patient, which arose 9 years earlier. Five of the 32 mutations (in ABCB11, HAUS3, SLC24A4, SNX4 and PALB2) were prevalent in the DNA of the primary tumour removed at diagnosis 9 years earlier, six (in KIF1C, USP28, MYH8, MORC1, KIAA1468 and RNASEH2A) were present at lower frequencies (1–13%), 19 were not detected in the primary tumour, and two were undetermined. The combined analysis of genome and transcriptome data revealed two new RNA-editing events that recode the amino acid sequence of SRP9 and COG3. Taken together, our data show that single nucleotide mutational heterogeneity can be a property of low or intermediate grade primary breast cancers and that significant evolution can occur with disease progression.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/92a38ec79f803a97da9942ff25f51539401ad7c9

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Citations in the corpus

Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. (2015, background): “Modes of Tumor Evolution and Cooperation between Tumor Subclones Longitudinal (Johnson et al., 2014; Mullighan et al., 2008; Shah et al., 2009), spatial (Aerts et al., 2014; Bashashati et al., 2013; Campbell et al., 2010; Gerlinger et al., 2012, 2014; Haffner et al., 2013; Navin et al., 2010, 2011;…”
Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development (2011, background): “Localized Genomic Rearrangement in a Patient with Chronic Lymphocytic Leukemia Advances in DNA sequencing have made it possible to identify the majority of somatically acquired genetic variants in cancer samples on a genome-wide basis (Ding et al., 2010; Mardis et al., 2009; Pleasance et al., 2010a,”
AlleleSeq: analysis of allele-specific expression and binding in a network framework (2011, methodology): “We ﬁnd that the accuracy of de novo SNP calling using reads from a functional genomic sequencing experiment such as RNA-Seq using a standard SNP caller package (e.g., SNVmix; Shah et al , 2009) is not as good as we would need for determining allele-speciﬁc behavior (see Supplementary Table 1 for the”
The Life History of 21 Breast Cancers (2012, background): “…are recognized to be mixtures of competing subclones, based on analyses of cancers sampled within a patient at different times (Ding et al., 2012; Shah et al., 2009), from different sites (Campbell et al., 2010; Ding et al., 2010; Yachida et al., 2010), at hypermutable genomic loci (Campbell et…”
Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal (2018, neutral): “To date, a number of primary-metastasis pairs have been analyzed retrospectively (Shah et al., 2009; Campbell et al., 2010; Yachida et al., 2010; Ding et al., 2010; Haffner et al., 2013; Bashashati et al., 2013; Lee et al., 2014; Gerlinger et al., 2014; Brastianos et al., 2015; Gundem et al., 2015;…”
Genome Remodeling in a Basal-like Breast Cancer Metastasis and Xenograft (2010, background): “One validated translocation t(4;9)(188855443;139022258), assembled in all three tumours, involved a long terminal repeat (LTR) from the ERVL-MaLR family on chromosome 4 and ABCA2 on chromosome 9.”