Tag: WES

Childhood Cancer Genomes

[PMID: 29489754] [Nature]

The landscape of genomic alterations across childhood cancers

“a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer.”

[PMID: 29489755] [Nature]

Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours

“a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events.”

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Dearly Drivers of Breast Cancer Mets

[PMID: 29480819] [Journal of Clinical Investigation]

Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer

“matched primary and metastatic breast cancers from 16 individuals and performed RNA-seq and DNA whole-exome sequencing on the primary tumor, 67 matched metastases (2–7 per patient), and a matched normal tissue comparator for each patient.” “predicted metastatic drivers by integrating known protein-protein networks with gene expression and DNA-seq data and the clonal evolution of metastasis within each patient.” “most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes… most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases.” Work from Charles Perou.

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.”