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Article
Open AccessGenome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population
Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study o...
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Article
Open AccessGermline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response
With the continued promise of immunotherapy for treating cancer, understanding how host genetics contributes to the tumor immune microenvironment (TIME) is essential to tailoring cancer screening and treatment...
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Article
Open AccessDNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer
Few studies have examined epigenetic age acceleration (AA), the difference between DNA methylation (DNAm) predicted age and chronological age, in relation to somatic genomic features in paired cancer and norma...
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Article
Open AccessGermline-somatic JAK2 interactions are associated with clonal expansion in myelofibrosis
Myelofibrosis is a rare myeloproliferative neoplasm (MPN) with high risk for progression to acute myeloid leukemia. Our integrated genomic analysis of up to 933 myelofibrosis cases identifies 6 germline suscep...
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Article
Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loc...
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Article
Novel MAPK/AKT-impairing germline NRAS variant identified in a melanoma-prone family
While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencin...
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Article
Open AccessMap** clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA
Clustered somatic mutations are common in cancer genomes and previous analyses reveal several types of clustered single-base substitutions, which include doublet- and multi-base substitutions1–5, diffuse hypermut...
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Article
Open AccessA large Canadian cohort provides insights into the genetic architecture of human hair colour
Hair colour is a polygenic phenotype that results from differences in the amount and ratio of melanins located in the hair bulb. Genome-wide association studies (GWAS) have identified many loci involved in the...
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Article
Open AccessThe ubiquitin ligase RNF5 determines acute myeloid leukemia growth and susceptibility to histone deacetylase inhibitors
Acute myeloid leukemia (AML) remains incurable, largely due to its resistance to conventional treatments. Here, we find that increased abundance of the ubiquitin ligase RNF5 contributes to AML development and ...
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Article
Genomic and evolutionary classification of lung cancer in never smokers
Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined b...
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Article
Open AccessWhole genome sequencing of skull-base chordoma reveals genomic alterations associated with recurrence and chordoma-specific survival
Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) c...
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Article
Open AccessThe genomic and epigenomic evolutionary history of papillary renal cell carcinomas
Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and...
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Article
Open AccessMassively parallel reporter assays of melanoma risk variants identify MX2 as a gene promoting melanoma
Genome-wide association studies (GWAS) have identified ~20 melanoma susceptibility loci, most of which are not functionally characterized. Here we report an approach integrating massively-parallel reporter ass...
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Article
Open AccessGenetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma
Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). Here, we investigate ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutatio...
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Article
Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility
Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified ...
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Article
Open AccessSiah2 control of T-regulatory cells limits anti-tumor immunity
Understanding the mechanisms underlying anti-tumor immunity is pivotal for improving immune-based cancer therapies. Here, we report that growth of BRAF-mutant melanoma cells is inhibited, up to complete reject...
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Article
Open AccessMicroparticles from tumors exposed to radiation promote immune evasion in part by PD-L1
Radiotherapy induces immune-related responses in cancer patients by various mechanisms. Here, we investigate the immunomodulatory role of tumor-derived microparticles (TMPs)—extracellular vesicles shed from tu...
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Article
Open AccessImmune gene expression profiling reveals heterogeneity in luminal breast tumors
Heterogeneity of immune gene expression patterns of luminal breast cancer (BC), which is clinically heterogeneous and overall considered as low immunogenic, has not been well studied especially in non-European...
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Article
Open AccessMeta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations
Association studies in recently admixed populations are extremely useful to identify the genetic architecture of pigmentation, due to their high genotypic and phenotypic variation. However, to date only four G...
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Article
Open AccessGut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5−/− mice
Accumulating evidence points to an important role for the gut microbiome in anti-tumor immunity. Here, we show that altered intestinal microbiota contributes to anti-tumor immunity, limiting tumor expansion. M...
