Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma.
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 E...
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doaj-b90805c653894f67a345f88ab5a3a9c72020-11-24T21:56:40ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-05-01135e100678710.1371/journal.pgen.1006787Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma.Lee D McDanielKarina L ConkriteXiao ChangMario CapassoZalman VaksmanDerek A OldridgeAnna ZachariouMillicent HornMaura DiamondCuiping HouAchille IolasconHakon HakonarsonNazneen RahmanMarcella DevotoSharon J DiskinNeuroblastoma 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.http://europepmc.org/articles/PMC5456408?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lee D McDaniel Karina L Conkrite Xiao Chang Mario Capasso Zalman Vaksman Derek A Oldridge Anna Zachariou Millicent Horn Maura Diamond Cuiping Hou Achille Iolascon Hakon Hakonarson Nazneen Rahman Marcella Devoto Sharon J Diskin |
spellingShingle |
Lee D McDaniel Karina L Conkrite Xiao Chang Mario Capasso Zalman Vaksman Derek A Oldridge Anna Zachariou Millicent Horn Maura Diamond Cuiping Hou Achille Iolascon Hakon Hakonarson Nazneen Rahman Marcella Devoto Sharon J Diskin Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma. PLoS Genetics |
author_facet |
Lee D McDaniel Karina L Conkrite Xiao Chang Mario Capasso Zalman Vaksman Derek A Oldridge Anna Zachariou Millicent Horn Maura Diamond Cuiping Hou Achille Iolascon Hakon Hakonarson Nazneen Rahman Marcella Devoto Sharon J Diskin |
author_sort |
Lee D McDaniel |
title |
Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma. |
title_short |
Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma. |
title_full |
Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma. |
title_fullStr |
Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma. |
title_full_unstemmed |
Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma. |
title_sort |
common variants upstream of mlf1 at 3q25 and within cpz at 4p16 associated with neuroblastoma. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2017-05-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC5456408?pdf=render |
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