Tag: CNV

CNA Evolution from Primary to CTCs

[PMID: 28487279] [Genome Research]

Single-cell sequencing deciphers a convergent evolution of copy number alterations from primary to circulating tumor cells

“Here, we studied genomic alterations in single primary tumor cells and circulating tumor cells (CTCs) from the same patient. Single-nucleotide variants (SNVs) in single cells from both samples occurred sporadically, whereas CNAs among primary tumor cells emerged accumulatively rather than abruptly, converging toward the CNA in CTCs. Focal CNAs affecting the MYC gene and the PTEN gene were observed only in a minor portion of primary tumor cells but were present in all CTCs, suggesting a strong selection toward metastasis. Single-cell structural variant (SV) analyses revealed a two-step mechanism, a complex rearrangement followed by gene amplification, for the simultaneous formation of anomalous CNAs in multiple chromosome regions.”

Clonality of Metastasis Breast Cancer

[PMID:28424200] [Clinical Cancer Research]

Whole exome sequencing of metaplastic breast carcinoma indicates monoclonality with associated ductal carcinoma component

In eight patients. “In each case, the tumor components have nearly identical landscapes of somatic mutation, implying that the differing histologies do not derive from genetic clonal divergence.”

[PMID:28429735] [Nature Communications]

Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations

“using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients” “two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common ‘metastatic precursor’. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour.”

CESAM

[PMID:27869826] [Nature Genetics]

Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking

“a computational framework termed cis expression structural alteration mapping (CESAM), which uses statistical concepts from expression quantitative trait locus mapping to integrate SCNAs, expression and chromatin interaction domain data to systematically identify SCNAs mediating gene dysregulation in cis. Using CESAM, we determined an estimate for the incidence of enhancer hijacking among the jumble of DNA rearrangements occurring in cancer genomes.” “Because we failed to reach a genomic inflation factor of

CNV Evolution in TNBC

[PMID:27526321] [Nature Genetics]

Punctuated copy number evolution and clonal stasis in triple-negative breast cancer

“We sequenced 1,000 single cells from tumors in 12 patients and identified 1–3 major clonal subpopulations in each tumor that shared a common evolutionary lineage. For each tumor, we also identified a minor subpopulation of non-clonal cells that were classified as metastable, pseudodiploid or chromazemic. Phylogenetic analysis and mathematical modeling suggest that these data are unlikely to be explained by the gradual accumulation of copy number events over time. In contrast, our data challenge the paradigm of gradual evolution, showing that the majority of copy number aberrations are acquired at the earliest stages of tumor evolution, in short punctuated bursts, followed by stable clonal expansions that form the tumor mass.” Work from Nicholas E Navin.

TNBC CNA Evoluation

[PMID:27526321] [Nature Genetics]

Punctuated copy number evolution and clonal stasis in triple-negative breast cancer

“We sequenced 1,000 single cells from tumors in 12 patients and identified 1–3 major clonal subpopulations in each tumor that shared a common evolutionary lineage. For each tumor, we also identified a minor subpopulation of non-clonal cells that were classified as metastable, pseudodiploid or chromazemic. Phylogenetic analysis and mathematical modeling suggest that these data are unlikely to be explained by the gradual accumulation of copy number events over time. In contrast, our data challenge the paradigm of gradual evolution, showing that the majority of copy number aberrations are acquired at the earliest stages of tumor evolution, in short punctuated bursts, followed by stable clonal expansions that form the tumor mass.” Work from Nicholas Navin.

EXCAVATOR2

[PMID: 27507884] [Nucleic Acids Research]

Enhanced copy number variants detection from whole-exome sequencing data using EXCAVATOR2

“more than 30% of WES data map outside the targeted regions and that these reads, usually discarded, can be exploited to enhance the identification of CNVs from WES experiments.””the first read count based tool that exploits all the reads produced by WES experiments to detect CNVs with a genome-wide resolution.”