17 Result(s)
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Mark T. A. Donoghue
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Article
Open AccessGenome-wide loss of heterozygosity predicts aggressive, treatment-refractory behavior in pituitary neuroendocrine tumors
Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical therapies, and an initial course of radiatio...
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Open AccessConvergent evolution of BRCA2 reversion mutations under therapeutic pressure by PARP inhibition and platinum chemotherapy
Reversion mutations that restore wild-type function of the BRCA gene have been described as a key mechanism of resistance to Poly(ADP-ribose) polymerase (PARP) inhibitor therapy in BRCA-associated cancers. Here, ...
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Open AccessReversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies
The association between loss of BRCA1/2 and a homologous recombination deficiency phenotype is lineage dependent. In BRCA-associated cancers such as breast, ovarian, pancreas and prostate, this phenotype confers ...
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Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer
The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggest...
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Open AccessOrdered and deterministic cancer genome evolution after p53 loss
Although p53 inactivation promotes genomic instability1 and presents a route to malignancy for more than half of all human cancers2,3, the patterns through which heterogenous TP53 (encoding human p53) mutant geno...
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Open AccessPilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma
PD-1 blockade (nivolumab) efficacy remains modest for metastatic sarcoma. In this paper, we present an open-label, non-randomized, non-comparative pilot study of bempegaldesleukin, a CD122-preferential interle...
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Open AccessAKT mutant allele-specific activation dictates pharmacologic sensitivities
AKT- a key molecular regulator of PI-3K signaling pathway, is somatically mutated in diverse solid cancer types, and aberrant AKT activation promotes altered cancer cell growth, survival, and metabolism1–8. The m...
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Anatomic position determines oncogenic specificity in melanoma
Oncogenic alterations to DNA are not transforming in all cellular contexts1,2. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determi...
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Discovery through clinical sequencing in oncology
The molecular characterization of tumors now informs clinical cancer care for many patients. This advent of molecular oncology has been driven by the expanding number of therapeutic biomarkers that can predict...
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Author Correction: Tumour lineage shapes BRCA-mediated phenotypes
An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Open AccessTransgenerational effects of inter-ploidy cross direction on reproduction and F2 seed development of Arabidopsis thaliana F1 hybrid triploids
Reproduction in triploid plants is important for understanding polyploid population dynamics. We show that genetically identical reciprocal F1 hybrid triploids can display transgenerational epigenetic effects ...
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Tumour lineage shapes BRCA-mediated phenotypes
Mutations in BRCA1 and BRCA2 predispose individuals to certain cancers1–3, and disease-specific screening and preventative strategies have reduced cancer mortality in affected patients4,5. These classical tumour-...
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Genome doubling shapes the evolution and prognosis of advanced cancers
Ploidy abnormalities are a hallmark of cancer, but their impact on the evolution and outcomes of cancers is unknown. Here, we identified whole-genome doubling (WGD) in the tumors of nearly 30% of 9,692 prospec...
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ALCAM is indirectly modulated by miR-125b in MCF7 cells
MicroRNA (miRNA) deregulation is associated with various cancers. Among an expanding list of cancer-related miRNAs, deregulation of miR-125b has been well documented in many cancers including breast. Based on ...
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Computational Identification and Evolutionary Relationships of the MicroRNA Gene Cluster miR-71/2 in Protostomes
MicroRNAs (miRNAs) are small noncoding RNA molecules which are processed into ~20–24 nt molecules that can regulate the gene expression post-transcriptionally. MiRNA gene clusters have been identified in a ran...
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Open AccessDraft genome sequence of pigeonpea (Cajanus cajan), an orphan legume crop of resource-poor farmers
Pigeonpea is an important protein source in many develo** countries, but limited genetic resources have constrained its improvement. The draft genome sequence of pigeonpea, the first for a nonindustrial crop...
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A phylogenetic approach to test for evidence of parental conflict or gene duplications associated with protein-encoding imprinted orthologous genes in placental mammals
There are multiple theories on the evolution of genomic imprinting. We investigated whether the molecular evolution of true orthologs of known imprinted genes provides support for theories based on gene duplic...
