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Signatures of mutational processes in human cancer
TLDR
It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
TLDR
BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.
Hallmarks of 'BRCAness' in sporadic cancers
TLDR
There are properties that define 'BRCAness' — that is, traits that some sporadic cancers share with those occurring in either BRCA1- or BRCa2-mutation carriers, which might have important implications for the clinical management of these cancers.
Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.
TLDR
Olaparib has few of the adverse effects of conventional chemotherapy, inhibits PARP, and has antitumor activity in cancer associated with the BRCA1 or BRCa2 mutation.
Landscape of somatic mutations in 560 breast cancer whole genome sequences
TLDR
This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operative, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
The landscape of cancer genes and mutational processes in breast cancer
TLDR
Strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade are found, and multiple mutational signatures are observed, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides.
Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition.
TLDR
The results indicate that PARP inhibition might be a useful therapeutic strategy not only for the treatment of BRCA mutation-associated tumors but also for a wider range of tumors bearing a variety of deficiencies in the HR pathway or displaying properties of 'BRCAness.
FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer.
TLDR
The data suggest that amplification and overexpression of FGFR1 may be a major contributor to poor prognosis in luminal-type breast cancers, driving anchorage-independent proliferation and endocrine therapy resistance.
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