Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Jan. 9, 2017

Abstract Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and aggressive disease. To understand this aggression, here we profile genomes methylomes localized PCa from 14 carriers deleterious germline ( -mutant PCa). We show that harbour genomic instability a mutational more closely resembles metastastic than shows epigenomic dysregulation MED12L / MED12 axis, which is frequently dysregulated metastatic castration-resistant (mCRPC). This enriched harbouring intraductal carcinoma (IDC). Microdissection sequencing IDC juxtaposed adjacent non-IDC invasive 10 patients demonstrates common ancestor to histopathologies. Overall castration-sensitive tumours uniquely aggressive, due de novo aberration genes usually disease, justifying initial treatment.

Language: Английский

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Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma

Blood, Journal Year: 2016, Volume and Issue: 128(13), P. 1735 - 1744

Published: Aug. 12, 2016

Language: Английский

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A cellular hierarchy framework for understanding heterogeneity and predicting drug response in acute myeloid leukemia

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(6), P. 1212 - 1223

Published: May 26, 2022

Language: Английский

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Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(10), P. 1456 - 1468

Published: Sept. 30, 2021

Language: Английский

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The evolution of lung cancer and impact of subclonal selection in TRACERx

Nature, Journal Year: 2023, Volume and Issue: 616(7957), P. 525 - 533

Published: April 12, 2023

Lung cancer is the leading cause of cancer-associated mortality worldwide

Language: Английский

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