bims-ovdlit 2022-12-11 papers

Nat Commun. 2022 Dec 03. 13(1): 7475

A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA.

Cell-free DNA (cfDNA) has the potential to inform tumor subtype classification and help guide clinical precision oncology. Here we develop Griffin, a framework for profiling nucleosome protection and accessibility from cfDNA to study the phenotype of tumors using as low as 0.1x coverage whole genome sequencing data. Griffin employs a GC correction procedure tailored to variable cfDNA fragment sizes, which generates a better representation of chromatin accessibility and improves the accuracy of cancer detection and tumor subtype classification. We demonstrate estrogen receptor subtyping from cfDNA in metastatic breast cancer. We predict estrogen receptor subtype in 139 patients with at least 5% detectable circulating tumor DNA with an area under the receive operator characteristic curve (AUC) of 0.89 and validate performance in independent cohorts (AUC = 0.96). In summary, Griffin is a framework for accurate tumor subtyping and can be generalizable to other cancer types for precision oncology applications.

DOI: https://doi.org/10.1038/s41467-022-35076-w

Nat Rev Clin Oncol. 2022 Dec 06.

New data confirm clinical utility of ctDNA.

Peter Sidaway.

DOI: https://doi.org/10.1038/s41571-022-00716-z

Nat Rev Genet. 2022 Dec 09.

Spatial biology of cancer evolution.

Zaira Seferbekova, Artem Lomakin, Lucy R Yates, Moritz Gerstung.

The natural history of cancers can be understood through the lens of evolution given that the driving forces of cancer development are mutation and selection of fitter clones. Cancer growth and progression are spatial processes that involve the breakdown of normal tissue organization, invasion and metastasis. For these reasons, spatial patterns are an integral part of histological tumour grading and staging as they measure the progression from normal to malignant disease. Furthermore, tumour cells are part of an ecosystem of tumour cells and their surrounding tumour microenvironment. A range of new spatial genomic, transcriptomic and proteomic technologies offers new avenues for the study of cancer evolution with great molecular and spatial detail. These methods enable precise characterizations of the tumour microenvironment, cellular interactions therein and micro-anatomical structures. In conjunction with spatial genomics, it emerges that tumours and microenvironments co-evolve, which helps explain observable patterns of heterogeneity and offers new routes for therapeutic interventions.

DOI: https://doi.org/10.1038/s41576-022-00553-x

Nat Genet. 2022 Dec;54(12): 1757

Genetic futurism.

DOI: https://doi.org/10.1038/s41588-022-01271-0

Nat Rev Cancer. 2022 Dec 09.

Biology, vulnerabilities and clinical applications of circulating tumour cells.

Alexander Ring, Bich Doan Nguyen-Sträuli, Andreas Wicki, Nicola Aceto.

In recent years, exceptional technological advances have enabled the identification and interrogation of rare circulating tumour cells (CTCs) from blood samples of patients, leading to new fields of research and fostering the promise for paradigm-changing, liquid biopsy-based clinical applications. Analysis of CTCs has revealed distinct biological phenotypes, including the presence of CTC clusters and the interaction between CTCs and immune or stromal cells, impacting metastasis formation and providing new insights into cancer vulnerabilities. Here we review the progress made in understanding biological features of CTCs and provide insight into exploiting these developments to design future clinical tools for improving the diagnosis and treatment of cancer.

DOI: https://doi.org/10.1038/s41568-022-00536-4

Nat Rev Genet. 2022 Dec 06.

A deep learning method to map tissue architecture.

Linda Koch.

DOI: https://doi.org/10.1038/s41576-022-00564-8