Tag: CNV

cfDNA Tumor Fraction and CNAs in Mets

[PMID: 29298117] [Journal of Clinical Oncology]

Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer

“low-coverage genome-wide sequencing of cfDNA from plasma.”


Workflow for WGS CNV

[PMID: 29304372] [American Journal of Human Genetics]

A Comprehensive Workflow for Read Depth-Based Identification of Copy-Number Variation from Whole-Genome Sequence Data

“Here, we used several datasets to empirically develop a detailed workflow for identifying germline CNVs >1 kb from short-read WGS data using read depth-based algorithms.”

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.”


[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.