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Distinct roles of BRCA2 in replication fork protection in response to hydroxyurea and DNA interstrand cross-links.
(COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2020-06-01)
DNA interstrand cross-links (ICLs) are a form of DNA damage that requires the interplay of a number of repair proteins including those of the Fanconi anemia (FA) and the homologous recombination (HR) pathways. Pathogenic ...
Genomic landscape of platinum resistant and sensitive testicular cancers.
(NATURE PUBLISHING GROUP, 2020-05-04)
While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and ...
Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial.
(ELSEVIER SCIENCE INC, 2020-01-01)
BACKGROUND: Metastatic castration-resistant prostate cancer is enriched in DNA damage response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and ...
Combined targeting of MEK and the glucocorticoid receptor for the treatment of RAS-mutant multiple myeloma.
(BMC, 2020-03-30)
BACKGROUND: Multiple myeloma (MM) remains incurable despite recent therapeutic advances. RAS mutations are frequently associated with relapsed/refractory disease. Efforts to target the mitogen-activated protein kinase ...
A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS.
(NATURE PUBLISHING GROUP, 2020-06-26)
Tumour-associated KRAS mutations are the most prevalent in the three RAS-family isoforms and involve many different amino-acids. Therefore, molecules able to interfere with mutant KRAS protein are potentially important for ...
PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation.
(NATURE PORTFOLIO, 2022-02-01)
The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase ...
Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.
(OXFORD UNIV PRESS INC, 2022-06-01)
We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an ...
Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells.
(BMC, 2022-06-10)
BACKGROUND: Development of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new ...
Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study.
(LIPPINCOTT WILLIAMS & WILKINS, 2022-10-01)
PURPOSE: Rhabdomyosarcomas (RMS) are rare neoplasms affecting children and young adults. Efforts to improve patient survival have been undermined by a lack of suitable disease markers. Plasma circulating tumor DNA (ctDNA) ...
Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.
(SPRINGER, 2020-02-01)
Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment ...