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Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma
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نویسنده
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mcdaniel l.d. ,conkrite k.l. ,chang x. ,capasso m. ,vaksman z. ,oldridge d.a. ,zachariou a. ,horn m. ,diamond m. ,huo c. ,iolascon a. ,hakonarson h. ,rahman n. ,devoto m. ,diskin s.j.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 5
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چکیده
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Neuroblastoma is a cancer of the developing sympathetic nervous system that most commonly presents in young children and accounts for approximately 12% of pediatric oncology deaths. here,we report on a genome-wide association study (gwas) in a discovery cohort or 2,101 cases and 4,202 controls of european ancestry. we identify two new association signals at 3q25 and 4p16 that replicated robustly in multiple independent cohorts comprising 1,163 cases and 4,396 controls (3q25: rs6441201 combined p = 1.2x10-11,odds ratio 1.23,95% ci:1.16–1.31; 4p16: rs3796727 combined p = 1.26x10-12,odds ratio 1.30,95% ci: 1.21–1.40). the 4p16 signal maps within the carboxypeptidase z (cpz) gene. the 3q25 signal resides within the arginine/serine-rich coiled-coil 1 (rsrc1) gene and upstream of the myeloid leukemia factor 1 (mlf1) gene. increased expression of mlf1 was observed in neuroblastoma cells homozygous for the rs6441201 risk allele (p = 0.02),and significant growth inhibition was observed upon depletion of mlf1 (p < 0.0001) in neuroblastoma cells. taken together,we show that common dna variants within cpz at 4p16 and upstream of mlf1 at 3q25 influence neuroblastoma susceptibility and mlf1 likely plays an important role in neuroblastoma tumorigenesis. © 2017 mcdaniel et al.
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آدرس
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division of oncology,children’s hospital of philadelphia,philadelphia,pa,united states,center for childhood cancer research,children’s hospital of philadelphia,philadelphia,pa, United States, division of oncology,children’s hospital of philadelphia,philadelphia,pa,united states,center for childhood cancer research,children’s hospital of philadelphia,philadelphia,pa, United States, the center for applied genomics,children’s hospital of philadelphia,philadelphia,pa, United States, university of naples federico ii,naples,italy,ceinge—biotecnologie avanzate,naples,italy,irccs sdn,istituto di ricerca diagnostica e nucleare,naples, Italy, division of oncology,children’s hospital of philadelphia,philadelphia,pa,united states,center for childhood cancer research,children’s hospital of philadelphia,philadelphia,pa,united states,department of biomedical and health informatics,children’s hospital of philadelphia,philadelphia,pa, United States, division of oncology,children’s hospital of philadelphia,philadelphia,pa,united states,center for childhood cancer research,children’s hospital of philadelphia,philadelphia,pa,united states,medical scientist training program,perelman school of medicine at the university of pennsylvania,philadelphia,pa, United States, the institute of cancer research,london, United Kingdom, division of oncology,children’s hospital of philadelphia,philadelphia,pa,united states,center for childhood cancer research,children’s hospital of philadelphia,philadelphia,pa, United States, division of oncology,children’s hospital of philadelphia,philadelphia,pa,united states,center for childhood cancer research,children’s hospital of philadelphia,philadelphia,pa, United States, the center for applied genomics,children’s hospital of philadelphia,philadelphia,pa, United States, university of naples federico ii,naples,italy,ceinge—biotecnologie avanzate,naples,italy,irccs sdn,istituto di ricerca diagnostica e nucleare,naples, Italy, the center for applied genomics,children’s hospital of philadelphia,philadelphia,pa,united states,department of pediatrics,perelman school of medicine,university of pennsylvania,philadelphia,pa,united states,division of genetics,the children’s hospital of philadelphia,philadelphia,pa, United States, the institute of cancer research,london, United Kingdom, division of genetics,the children’s hospital of philadelphia,philadelphia,pa,united states,university of rome la sapienza,department of molecular medicine,rome,italy,department of biostatistics and epidemiology,perelman school of medicine,university of pennsylvania,philadelphia,pa, United States, division of oncology,children’s hospital of philadelphia,philadelphia,pa,united states,center for childhood cancer research,children’s hospital of philadelphia,philadelphia,pa,united states,department of biomedical and health informatics,children’s hospital of philadelphia,philadelphia,pa,united states,abramson family cancer research institute,perelman school of medicine at the university of pennsylvania,philadelphia,pa, United States
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Authors
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