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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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Article
BRAF — a tumour-agnostic drug target with lineage-specific dependencies
In June 2022, the FDA granted Accelerated Approval to the BRAF inhibitor dabrafenib in combination with the MEK inhibitor trametinib for the treatment of adult and paediatric patients (≥6 years of age) with un...
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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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Article
Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade
Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia developme...
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Article
Clonal evolution during metastatic spread in high-risk neuroblastoma
Patients with high-risk neuroblastoma generally present with widely metastatic disease and often relapse despite intensive therapy. As most studies to date focused on diagnosis-relapse pairs, our understanding...
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Open AccessAntitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers
HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs). Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor kinase activation and has a...
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Open AccessAuthor Correction: FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation
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Open AccessFOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation
Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differ...
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Article
Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer
Circulating tumor DNA (ctDNA) sequencing guides therapy decisions but has been studied mostly in small cohorts without sufficient follow-up to determine its influence on overall survival. We prospectively foll...
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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 AccessClinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets
The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma sub...
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Correction: Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma
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Article
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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Article
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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Open AccessMolecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights
Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed w...
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Open AccessHER2 + breast cancers evade anti-HER2 therapy via a switch in driver pathway
Inhibition of HER2 in HER2-amplified breast cancer has been remarkably successful clinically, as demonstrated by the efficacy of HER-kinase inhibitors and HER2-antibody treatments. Whilst resistance to HER2 in...
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Article
The context-specific role of germline pathogenicity in tumorigenesis
Human cancers arise from environmental, heritable and somatic factors, but how these mechanisms interact in tumorigenesis is poorly understood. Studying 17,152 prospectively sequenced patients with cancer, we ...
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Clinical cancer genomic profiling
Technological innovation and rapid reduction in sequencing costs have enabled the genomic profiling of hundreds of cancer-associated genes as a component of routine cancer care. Tumour genomic profiling can re...
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Open AccessEnhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS
Circulating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulatin...
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Open AccessTumor fraction-guided cell-free DNA profiling in metastatic solid tumor patients
Cell-free DNA (cfDNA) profiling is increasingly used to guide cancer care, yet mutations are not always identified. The ability to detect somatic mutations in plasma depends on both assay sensitivity and the f...
