Tag: Cancer Evolution

ECdetect

[PMID:28178237] [Nature]

Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity

“We performed whole-genome sequencing, structural modelling and cytogenetic analyses of 17 different cancer types, including analysis of the structure and function of chromosomes during metaphase of 2,572 dividing cells, and developed a software package called ECdetect to conduct unbiased, integrated ecDNA detection and analysis. Here we show that ecDNA was found in nearly half of human cancers; its frequency varied by tumour type, but it was almost never found in normal cells. Driver oncogenes were amplified most commonly in ecDNA, thereby increasing transcript level.”

Purifying Selection in Cancer

[PMID:28027311] [PLoS Genetics]

Somatic Mutation Patterns in Hemizygous Genomic Regions Unveil Purifying Selection during Tumor Evolution

“cancer cells additionally depend on a large number of genes involved in basic cellular processes. While such genes should in theory be subject to strong purifying (negative) selection against damaging somatic mutations, these patterns have been elusive and purifying selection remains inadequately explored in cancer. Here, we hypothesized that purifying selection should be evident in hemizygous genomic regions, where damaging mutations cannot be compensated for by healthy alleles.”

DCCs

[PMID:27974798] [Nature]

Mechanism of early dissemination and metastasis in Her2+ mammary cancer

[PMID:27974799] [Nature]

Early dissemination seeds metastasis in breast cancer

“progesterone-induced signalling triggers migration of cancer cells from early lesions shortly after HER2 activation, but promotes proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by increased HER2 expression and tumour-cell density involving microRNA-mediated progesterone receptor downregulation, and was reversible. Cells from early, low-density lesions displayed more stemness features, migrated more and founded more metastases than cells from dense, advanced tumours.”

[PMID:27974802] [Nature]

Metastasis: Pathways of parallel progression

On the contrary, a recent paper supports the model of late dissemination of breast cancer cells to the bone marrow. Work from Kevin White and Peter Van Loo.

[PMID:27931250] [Genome Biology]

Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing