Dataset Information

Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.

ABSTRACT: Circulating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient's cancer is evolving in order to aid clinical decisions remains difficult. This is because ctDNA is a mix of fragmented alleles, and the contribution of different cancer deposits to ctDNA is largely unknown. Profiling ctDNA almost invariably requires prior knowledge of what genomic alterations to track. Here, we leverage on a rapid autopsy programme to demonstrate that unbiased genomic characterisation of several metastatic sites and concomitant ctDNA profiling at whole-genome resolution reveals the extent to which ctDNA is representative of widespread disease. We also present a methylation profiling method that allows tracking evolutionary changes in ctDNA at single-molecule resolution without prior knowledge. These results have critical implications for the use of liquid biopsies to monitor cancer evolution in humans and guide treatment.

SUBMITTER: Cresswell GD

PROVIDER: S-EPMC7101390 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.

Cresswell George D GD Nichol Daniel D Spiteri Inmaculada I Tari Haider H Zapata Luis L Heide Timon T Maley Carlo C CC Magnani Luca L Schiavon Gaia G Ashworth Alan A Barry Peter P Sottoriva Andrea A

Nature communications 20200327 1

Circulating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient's cancer is evolving in order to aid clinical decisions remains difficult. This is because ctDNA is a mix of fragmented alleles, and the contribution of different cancer deposits to ctDNA is largely unknown. Profiling ctDNA almost invariably requires prior knowledge of what genomic alterations to ...[more]

PMID: 32221288

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Project description:Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland and affect more than 12,000 individuals annually. Several hundred of these patients are likely to carry known genetic mutations associated with HBOC or LS. Genetic testing for hereditary susceptibility to cancer can prevent many cancer deaths through early identification and engagement in high-risk management care that involves intensive surveillance, chemoprevention and/or prophylactic surgery. However, current rates of genetic testing indicate that many Swiss mutation carriers and their family members do not use cancer genetic services (counseling and/or testing), either due to lack of coordination of care or due to lack of communication about the mutation among family members. Cascade screening identifies and tests family members of a known mutation carrier. It determines whether asymptomatic family members are carriers of the identified mutation and proposes management options to reduce harmful outcomes. Robust evidence of basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for HBOC and LS. However, translation of this knowledge into public health interventions is lacking. Specific Aims of the CASCADE study are: 1. Survey Index Patients diagnosed with HBOC or LS from clinic-based genetic testing records and determine their cancer status and surveillance practices; needs for coordination of medical care; psychosocial needs; patient-provider and patient-family communication needs; quality of life; willingness to serve as advocates for cancer genetic services for blood relatives. 2. Survey first- and second-degree relatives, and first cousins identified from pedigrees and/or family history records of HBOC and LS Index Patients and determine their cancer and mutation status; cancer surveillance practices; needs for coordination of medical care; barriers and facilitators to using cancer genetic services; psychosocial needs; patient-provider and patient-family communication needs; quality of life; willingness to participate in a study designed to increase use of cancer genetic services. 3. Explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and blood relatives.

Dataset Information

Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.

Publications

Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.

Similar Datasets

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