Tag: WES

ichorCNA

[PMID: 29109393] [Nature Communications]

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

“software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers.” Work from Gad Getz and Matthew Meyerson.

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Subclonal Evolution of Resistant Cancer Phenotypes

[PMID: 29093439] [Nature Communications]

Combating subclonal evolution of resistant cancer phenotypes

“track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment” “These findings highlight cancer’s ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves.”

Genomes of Metastatic Cancer

[PMID: 28783718] [Nature]

Integrative clinical genomics of metastatic cancer

“whole-exome and -transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site. The most prevalent genes somatically altered in metastatic cancer included TP53CDKN2APTENPIK3CA, and RB1. Putative pathogenic germline variants were present in 12.2% of cases of which 75% were related to defects in DNA repair.”

MutSigNC

[PMID:28658208] [Nature]

Recurrent and functional regulatory mutations in breast cancer

“deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters.” “promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions.” Work from Gad Getz.

[PMID:28658210] [Nature]

Cancer genomics: Less is more in the hunt for driver mutations

“The authors’ power analysis (statistical calculations estimating the sample numbers needed to detect an effect of a given size) indicated that more than 90% of drivers could be reliably identified if they occurred in at least 10% of the 360 samples studied, but only 70% of drivers present in 5%of patients would be identified”

Melanoma Subtypes

[PMID:28467829] [Nature]

Whole-genome landscapes of major melanoma subtypes

 

“Significantly mutated genes included BRAF, CDKN2A, NRAS and TP53 in cutaneous melanoma, BRAF, NRAS and NF1 in acral melanoma and SF3B1 in mucosal melanoma. Mutations affecting the TERT promoter were the most frequent of all; however, neither they nor ATRX mutations, which correlate with alternative telomere lengthening, were associated with greater telomere length.” “Telomere length was not correlated with melanoma subtype, chromothripsis or breakage–fusion–bridge events.”

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.”